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  <H5 align="left" style="page-break-before:always"><A HREF="#toc">Table of Contents</A></H5><P>
  <DIV style="font-family: 'Times New Roman',Times,serif">
  
  <DIV align="center" style="font-size: 10pt; margin-top: 12pt"><B>As filed with the Securities and Exchange Commission on
  October&nbsp;3, 2008</B></DIV>
  
  
  <DIV align="right" style="font-size: 10pt; margin-top: 6pt"><B>Registration No.&nbsp;333- </B>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
  </DIV>
  
  
  <DIV style="width: 100%; border-bottom: 2pt solid black; font-size: 1pt">&nbsp;</DIV>
  <DIV style="width: 100%; border-bottom: 1pt solid black; font-size: 1pt">&nbsp;</DIV>
  
  
  
  
  
  
  <DIV align="center" style="font-size: 14pt; margin-top: 12pt"><B>UNITED STATES<BR>
  SECURITIES AND EXCHANGE COMMISSION</B>
  </DIV>
  
  <DIV align="center" style="font-size: 12pt"><B>Washington, D.C. 20549</B>
  </DIV>
  
  <DIV align="center" style="font-size: 18pt; margin-top: 12pt"><B>FORM S-8</B>
  </DIV>
  
  
  <DIV align="center" style="font-size: 12pt; margin-top: 12pt"><B>REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933</B>
  </DIV>
  
  <DIV align="center" style="font-size: 24pt; margin-top: 12pt"><B>RXi PHARMACEUTICALS CORPORATION</B>
  </DIV>
  
  <DIV align="center" style="font-size: 10pt">(Exact name of registrant as specified in its charter)</DIV>
  
  
  <DIV align="center">
  <TABLE style="font-size: 10pt" cellspacing="0" border="0" cellpadding="0" width="100%">
  <!-- Begin Table Head -->
  <TR valign="bottom">
      <TD width="47%">&nbsp;</TD>
      <TD width="5%">&nbsp;</TD>
      <TD width="47%">&nbsp;</TD>
  </TR>
  <!-- End Table Head -->
  <!-- Begin Table Body -->
  <TR valign="bottom">
      <TD align="center" valign="top"><B>Delaware</B>
  </TD>
      <TD>&nbsp;</TD>
      <TD align="center" valign="top"><B>20-8099512</B></TD>
  </TR>
  <TR valign="bottom">
      <TD align="center" valign="top">(State or other jurisdiction <BR>
  of incorporation or organization)
  </TD>
      <TD>&nbsp;</TD>
      <TD align="center" valign="top">(I.R.S Employer Identification No.)</TD>
  </TR>
  <TR valign="bottom"><!-- Blank Space -->
      <TD align="center" valign="top">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD align="center" valign="top">&nbsp;</TD>
  </TR>
  <TR valign="bottom">
      <TD align="center" valign="top"><B>60 Prescott Street, Worcester, Massachusetts</B>
  </TD>
      <TD>&nbsp;</TD>
      <TD align="center" valign="top"><B>01605</B></TD>
  </TR>
  <TR valign="bottom">
      <TD align="center" valign="top">(Address of Principal Executive Offices)
  </TD>
      <TD>&nbsp;</TD>
      <TD align="center" valign="top">(Zip Code)</TD>
  </TR>
  <!-- End Table Body -->
  </TABLE>
  </DIV>
  
  <DIV align="center" style="font-size: 10pt; margin-top: 12pt"><B>RXi Pharmaceuticals Corporation 2007 Incentive Plan</B></DIV>
  
  <DIV align="center" style="font-size: 10pt">(Full title of the plan)</DIV>
  
  
  <DIV align="center" style="font-size: 10pt; margin-top: 12pt"><B>Tod Woolf, Ph.D.<BR>
  Chief Executive Officer<BR>
  RXi Pharmaceuticals Corporation<BR>
  60 Prescott Street<BR>
  Worcester, Massachusetts 01605<BR>
  (508)&nbsp;767-3861</B></DIV>
  
  <DIV align="center" style="font-size: 10pt; margin-top: 12pt"><B>With copies to:<BR>
  Marc A. Rubenstein, Esq.<BR>
  Ropes &#038; Gray LLP<BR>
  One International Place<BR>
  Boston, Massachusetts 02110<BR>
  (617)&nbsp;951-7000</B></DIV>
  
  <DIV align="center" style="font-size: 10pt; margin-top: 6pt">(Name, address, and telephone number, including area code, of agent for service)</DIV>
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer or a smaller reporting company. See the definitions of &#147;large accelerated filer,&#148; &#147;accelerated filer&#148; and &#147;smaller reporting company&#148; in Rule 12b-2 of the Exchange Act. (Check one):</DIV>
  
   <TABLE width="100%" style="font-size: 10pt; margin-top: 0pt"><TR><TD>Large accelerated filer&nbsp;
  <FONT face="Wingdings">&#111;</FONT></TD><TD align="center">
  Accelerated filer&nbsp;<FONT face="Wingdings">&#111;</FONT>&nbsp;</TD>
  <TD align="center">Non-accelerated filer&nbsp;<FONT face="Wingdings">&#111;</FONT>
  <BR>(Do not check if a smaller reporting company)</TD><TD align="right">
  Smaller reporting company&nbsp;<FONT face="Wingdings">&#254;</FONT></TD></TR></TABLE>
  
  
  
  
  
  
  <DIV align="center" style="font-size: 10pt; margin-top: 18pt"><B>CALCULATION OF REGISTRATION FEE</B>
  </DIV>
  
  <DIV align="center">
  <TABLE style="font-size: 10pt" cellspacing="0" border="0" cellpadding="0" width="100%">
  <!-- Begin Table Head -->
  <TR style="font-size: 1pt" valign="bottom">
      <TD width="1%">&nbsp;</TD>
      <TD width="36%">&nbsp;</TD>
      <TD width="2%">&nbsp;</TD><!-- VRule -->
      <TD width="2%">&nbsp;</TD>
      <TD width="7%">&nbsp;</TD>
      <TD width="1%">&nbsp;</TD>
      <TD width="8%">&nbsp;</TD>
      <TD width="2%">&nbsp;</TD><!-- VRule -->
      <TD width="2%">&nbsp;</TD>
      <TD width="3%">&nbsp;</TD>
      <TD width="1%">&nbsp;</TD>
      <TD width="3%">&nbsp;</TD>
      <TD width="2%">&nbsp;</TD><!-- VRule -->
      <TD width="2%">&nbsp;</TD>
      <TD width="9%">&nbsp;</TD>
      <TD width="1%">&nbsp;</TD>
      <TD width="9%">&nbsp;</TD>
      <TD width="2%">&nbsp;</TD><!-- VRule -->
      <TD width="2%">&nbsp;</TD>
      <TD width="1%">&nbsp;</TD>
      <TD width="1%">&nbsp;</TD>
      <TD width="2%">&nbsp;</TD>
  
      <TD width="1%">&nbsp;</TD>
  </TR>
  <TR style="font-size: 1px" valign="bottom">
      <TD nowrap align="left" colspan="23" style="border-bottom: 3px double #000000">&nbsp;</TD>
  </TR>
  
  <TR style="font-size: 8pt" valign="bottom">    <TD width="1%">&nbsp;</TD>
  
      <TD>&nbsp;</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center" colspan="3">Proposed maximum</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center" colspan="3">&nbsp;</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center" colspan="3">&nbsp;</TD>
      <TD width="1%">&nbsp;</TD>
  </TR>
  <TR style="font-size: 8pt" valign="bottom">    <TD width="1%">&nbsp;</TD>
  
      <TD nowrap align="center">Title of each class of</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center" colspan="3">Amount to be</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center" colspan="3">offering price</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center" colspan="3">Proposed maximum</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center" colspan="3">Amount of</TD>
      <TD width="1%">&nbsp;</TD>
  </TR>
  <TR style="font-size: 8pt" valign="bottom">    <TD width="1%">&nbsp;</TD>
  
      <TD nowrap align="center">securities to be registered</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center" colspan="3">registered (1)</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center" colspan="3">per share (2)</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center" colspan="3">aggregate offering price</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center" colspan="3">registration fee</TD>
      <TD width="1%">&nbsp;</TD>
  </TR>
  
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      <TD width="1%" style="border-top: 2px solid #000000">&nbsp;</TD>
                      <TD valign="top" style="border-top: 2px solid #000000"><DIV style="margin-left:0px; text-indent:-0px">Common Stock,
  $.0001 par value
  per share
  </DIV></TD>
      <TD style="border-right: 2px solid #000000; border-top: 2px solid #000000">&nbsp;</TD>
      <TD style="border-top: 2px solid #000000">&nbsp;</TD>
      <TD nowrap align="right" valign="bottom" style="border-top: 2px solid #000000">&nbsp;</TD>
      <TD align="right" valign="bottom" style="border-top: 2px solid #000000">1,000,000</TD>
      <TD nowrap valign="bottom" style="border-top: 2px solid #000000">&nbsp;</TD>
      <TD style="border-right: 2px solid #000000; border-top: 2px solid #000000">&nbsp;</TD>
      <TD style="border-top: 2px solid #000000">&nbsp;</TD>
      <TD nowrap align="right" valign="bottom" style="border-top: 2px solid #000000">$</TD>
      <TD align="right" valign="bottom" style="border-top: 2px solid #000000">8.00</TD>
      <TD nowrap valign="bottom" style="border-top: 2px solid #000000">&nbsp;</TD>
      <TD style="border-right: 2px solid #000000; border-top: 2px solid #000000">&nbsp;</TD>
      <TD style="border-top: 2px solid #000000">&nbsp;</TD>
      <TD nowrap align="right" valign="bottom" style="border-top: 2px solid #000000">$</TD>
      <TD align="right" valign="bottom" style="border-top: 2px solid #000000">8,000,000</TD>
      <TD nowrap valign="bottom" style="border-top: 2px solid #000000">&nbsp;</TD>
      <TD style="border-right: 2px solid #000000; border-top: 2px solid #000000">&nbsp;</TD>
      <TD style="border-top: 2px solid #000000">&nbsp;</TD>
  
      <TD align="center" colspan="3" valign="bottom" style="border-top: 2px solid #000000">$314</TD>
  
      <TD width="1%" style="border-top: 2px solid #000000">&nbsp;</TD>
  </TR>
  <TR style="font-size: 1px" valign="bottom">
      <TD nowrap align="left" colspan="23" style="border-top: 3px double #000000">&nbsp;</TD>
  </TR>
  
  <!-- End Table Body -->
  </TABLE>
  </DIV>
  
  
  
  <DIV style="margin-top: 3pt">
  <TABLE width="100%" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt">
  <TR>
      <TD width="3%"></TD>
      <TD width="1%"></TD>
      <TD width="96"></TD>
  </TR>
  <TR valign="top">
      <TD nowrap align="left">(1)</TD>
      <TD>&nbsp;</TD>
      <TD>Pursuant to Rule 416(a) under the Securities Act of 1933, this registration statement also
  covers such additional shares as may be required pursuant to RXi Pharmaceuticals Corporation&#146;s 2007
  Incentive Plan in the event of a stock dividend, stock split, recapitalization or other similar
  change in the common stock.</TD>
  </TR>
  
  <TR style="font-size: 3pt"><TD>&nbsp;</TD></TR>
  
  <TR valign="top">
      <TD nowrap align="left">(2)</TD>
      <TD>&nbsp;</TD>
      <TD>The offering price of $8.00 per share has been estimated solely for the purpose of determining
  the registration fee pursuant to Rule 457(c) and 457(h)(1) on the basis of the average high and low
  prices of the Common Stock, as reported on the Nasdaq Capital Market on September&nbsp;29, 2008.</TD>
  </TR>
  
  </TABLE>
  </DIV>
  
  
  <DIV style="width: 100%; border-bottom: 1pt solid black; margin-top: 10pt; font-size: 1pt">&nbsp;</DIV>
  <DIV style="width: 100%; border-bottom: 2pt solid black; font-size: 1pt">&nbsp;</DIV>
  
  
  
  
  
  <P align="center" style="font-size: 10pt"><!-- Folio -->&nbsp;<!-- /Folio -->
  </DIV>
  
  <!-- PAGEBREAK -->
  <P><HR noshade><P>
  
  <DIV style="font-family: 'Times New Roman',Times,serif">
  
  
  
  
  
  
  
  
  <!-- TOC -->
  <A name="toc"><DIV align="CENTER" style="page-break-before:always"><U><B>TABLE OF CONTENTS</B></U></DIV></A>
  
  <P><CENTER>
  <TABLE border="0" width="90%" cellpadding="0" cellspacing="0">
  <TR>
  	<TD width="3%"></TD>
  	<TD width="3%"></TD>
  	<TD width="3%"></TD>
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  	<TD width="3%"></TD>
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  	<TD width="3%"></TD>
  	<TD width="76%"></TD>
  </TR>
  <TR><TD></TD><TD colspan="8"><A HREF="#000">ITEM 5. Interest of Named Experts and Counsel.</A></TD></TR>
  <TR><TD></TD><TD colspan="8"><A HREF="#001">ITEM 6. Indemnification of Directors and Officers.</A></TD></TR>
  <TR><TD></TD><TD colspan="8"><A HREF="#002">ITEM 7. Exemption from Registration Claimed.</A></TD></TR>
  <TR><TD></TD><TD colspan="8"><A HREF="#003">ITEM 8. Exhibits.</A></TD></TR>
  <TR><TD></TD><TD colspan="8"><A HREF="#004">ITEM 9. Undertakings.</A></TD></TR>
  <TR><TD colspan="9"><A HREF="#005">SIGNATURES</A></TD></TR>
  <TR><TD colspan="9"><A HREF="#006">EXHIBIT INDEX</A></TD></TR>
  <TR><TD colspan="9"><A HREF="b72438rxexv5w1.htm">EX-5.1 Opinion of Ropes & Gray LLP</A></TD></TR>
  <TR><TD colspan="9"><A HREF="b72438rxexv23w1.htm">EX-23.1 Consent of BDO Seidman, LLP, Independent Registered Public Accounting Firm.</A></TD></TR>
  </TABLE>
  </CENTER>
  <!-- /TOC -->
  <P><HR noshade><P>
  <H5 align="left" style="page-break-before:always"><A HREF="#toc">Table of Contents</A></H5><P>
  
  
  
  
  
  
  
  
  
  <DIV align="center" style="font-size: 10pt; margin-top: 18pt"><B>EXPLANATORY NOTE</B>
  </DIV>
  
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;This Registration Statement is being filed to increase the number of shares of common stock,
  par value $.0001 per share, of RXi Pharmaceuticals Corporation that may be issued and sold pursuant
  to the RXi Pharmaceuticals Corporation&#146;s 2007 Incentive Plan by an additional 1,000,000 shares.
  Pursuant to Instruction E to Form S-8, the Registrant incorporates by reference into this
  Registration Statement the entire contents of its Registration Statement on Form S-8 (File No.
  333-151154) filed with the Securities and Exchange Commission on May&nbsp;23, 2008, except with respect
  to Items 5, 6, 7, 8 and 9.
  </DIV>
  <!-- link2 "ITEM 5. Interest of Named Experts and Counsel." -->
  <DIV align="left"><A NAME="000"></A></DIV>
  
  <DIV align="left" style="font-size: 10pt; margin-top: 12pt"><B>ITEM 5. Interest of Named Experts and Counsel.</B>
  </DIV>
  
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Not applicable.
  </DIV>
  <!-- link2 "ITEM 6. Indemnification of Directors and Officers." -->
  <DIV align="left"><A NAME="001"></A></DIV>
  
  <DIV align="left" style="font-size: 10pt; margin-top: 12pt"><B>ITEM 6. Indemnification of Directors and Officers.</B>
  </DIV>
  
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Section&nbsp;145 of the Delaware General Corporation Law provides that a corporation may indemnify
  any person who was or is a party or is threatened to be made a party to any threatened, pending or
  completed action, suit or proceeding, whether civil, criminal, administrative or investigative,
  other than an action by or in the right of the corporation, by reason of the fact that the person
  is or was a director, officer, employee or agent of the corporation or is or was serving at the
  corporation&#146;s request as a director, officer, employee or agent of another corporation,
  partnership, joint venture, trust or other enterprise, against expenses, including attorneys&#146; fees,
  judgments, fines and amounts paid in settlement actually and reasonably incurred by the person in
  connection with the action, suit or proceeding if the person acted in good faith and in a manner
  the person reasonably believed to be in or not opposed to the best interests of the corporation,
  and, with respect to any criminal action or proceeding, had no reasonable cause to believe the
  person&#146;s conduct was unlawful. The power to indemnify applies to actions brought by or in the right
  of the corporation as well, but only to the extent of expenses, including attorneys&#146; fees but
  excluding judgments, fines and amounts paid in settlement, actually and reasonably incurred by the
  person in connection with the defense or settlement of the action or suit if the person acted in
  good faith and in a manner the person reasonably believed to be in or not opposed to the best
  interests of the corporation and except that no indemnification shall be made in respect of any
  claim, issue or matter as to which such person shall have been adjudged to be liable to the
  corporation unless and only to the extent that a court of competent jurisdiction shall determine
  that such indemnity is proper.
  </DIV>
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Section&nbsp;145(g) of the Delaware General Corporation Law provides that a corporation shall have
  the power to purchase and maintain insurance on behalf of its officers, directors, employees and
  agents, against any liability asserted against and incurred by such persons in any such capacity.
  </DIV>
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Section&nbsp;102(b)(7) of the General Corporation Law of the State of Delaware provides that a
  corporation may eliminate or limit the personal liability of a director to the corporation or its
  stockholders for monetary damages for breach of fiduciary duty as a director, provided that such
  provision shall not eliminate or limit the liability of a director (i)&nbsp;for any breach of the
  director&#146;s duty of loyalty to the corporation or its stockholders, (ii)&nbsp;for acts or omissions not
  in good faith or which involve intentional misconduct or a knowing violation of law, (iii)&nbsp;under
  Section&nbsp;174 of the General Corporation Law of the State of Delaware, or (iv)&nbsp;for any transaction
  from which the director derived an improper personal benefit. No such provision shall eliminate or
  limit the liability of a director for any act or omission occurring prior to the date when such
  provision becomes effective.
  </DIV>
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Our Amended and Restated Certificate of Incorporation provides that our directors shall not be
  liable to the Registrant or its stockholders for monetary damages for breach of fiduciary duty as a
  director, except to the extent that the exculpation from liabilities is not permitted under the
  Delaware General Corporation Law as in effect at the time such liability is determined. In
  addition, our Amended and Restated Certificate of Incorporation provides that we shall indemnify
  our directors to the fullest extent permitted by the laws of the State of Delaware. We have entered
  into indemnification agreements with each of our non-employee directors that provide for
  indemnification and expense advancement to the fullest extent permitted by the laws of the State of
  Delaware.
  </DIV>
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Our Amended and Restated Certificate of Incorporation provides that we may purchase and
  maintain insurance policies on behalf of our directors and officers against specified liabilities
  for actions taken in their
  </DIV>
  
  <P align="center" style="font-size: 10pt"><!-- Folio -->&nbsp;<!-- /Folio -->
  </DIV>
  
  <!-- PAGEBREAK -->
  <P><HR noshade><P>
  <H5 align="left" style="page-break-before:always"><A HREF="#toc">Table of Contents</A></H5><P>
  
  <DIV style="font-family: 'Times New Roman',Times,serif">
  
  
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">capacities as such, including liabilities under the Securities Act. We have obtained directors and
  officers&#146; liability insurance to cover liabilities our directors and officers may incur in
  connection with their services to the Registrant.
  </DIV>
  <!-- link2 "ITEM 7. Exemption from Registration Claimed." -->
  <DIV align="left"><A NAME="002"></A></DIV>
  
  <DIV align="left" style="font-size: 10pt; margin-top: 12pt"><B>ITEM 7. Exemption from Registration Claimed.</B>
  </DIV>
  
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Not applicable.
  </DIV>
  <!-- link2 "ITEM 8. Exhibits." -->
  <DIV align="left"><A NAME="003"></A></DIV>
  
  <DIV align="left" style="font-size: 10pt; margin-top: 12pt"><B>ITEM 8. Exhibits.</B>
  </DIV>
  
  <DIV align="center">
  <TABLE style="font-size: 10pt" cellspacing="0" border="0" cellpadding="0" width="100%">
  <!-- Begin Table Head -->
  <TR valign="bottom">
      <TD width="6%">&nbsp;</TD>
      <TD width="2%">&nbsp;</TD>
      <TD width="92%">&nbsp;</TD>
  </TR>
  <!-- End Table Head -->
  <!-- Begin Table Body -->
  <TR valign="bottom">
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">4.1
  </DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">2007 Incentive Plan (previously filed as Exhibit&nbsp;10.19 to the Registration
  Statement on Form&nbsp;S-1, as amended, No.&nbsp;333-147009, and incorporated herein by
  reference).</TD>
  </TR>
  <TR valign="bottom"><!-- Blank Space -->
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
  </TR>
  <TR valign="bottom">
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">4.2
  </DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">Amended and Restated Certificate of Incorporation (previously filed as
  Exhibit&nbsp;3.1 to the Registration Statement on Form&nbsp;S-1, as amended, No.
  333-147009, and incorporated herein by reference).</TD>
  </TR>
  <TR valign="bottom"><!-- Blank Space -->
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
  </TR>
  <TR valign="bottom">
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">4.3
  </DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">Amended and Restated Bylaws, as amended (previously filed as Exhibit&nbsp;3.2 to
  the Registration Statement on Form&nbsp;S-1, as amended, No.&nbsp;333-147009, and
  incorporated herein by reference).</TD>
  </TR>
  <TR valign="bottom"><!-- Blank Space -->
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
  </TR>
  <TR valign="bottom">
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">5.1
  </DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">Opinion of Ropes &#038; Gray LLP.</TD>
  </TR>
  <TR valign="bottom"><!-- Blank Space -->
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
  </TR>
  <TR valign="bottom">
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">23.1
  </DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">Consent of BDO Seidman, LLP, Independent Registered Public Accounting Firm.</TD>
  </TR>
  <TR valign="bottom"><!-- Blank Space -->
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
  </TR>
  <TR valign="bottom">
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">23.2
  </DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">Consent of Ropes &#038; Gray, LLP (see Exhibit&nbsp;5.1).</TD>
  </TR>
  <TR valign="bottom"><!-- Blank Space -->
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
  </TR>
  <TR valign="bottom">
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">24.1
  </DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">Power of Attorney (included on the signature page hereto).</TD>
  </TR>
  <!-- End Table Body -->
  </TABLE>
  </DIV>
  
  <!-- link2 "ITEM 9. Undertakings." -->
  <DIV align="left"><A NAME="004"></A></DIV>
  
  <DIV align="left" style="font-size: 10pt; margin-top: 12pt"><B>ITEM 9. Undertakings.</B>
  </DIV>
  
  
  <DIV style="margin-top: 6pt">
  <TABLE width="100%" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt">
  
  <TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="3%" nowrap align="left">(a)</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>The undersigned Registrant hereby undertakes:</TD>
  </TR>
  
  </TABLE>
  </DIV>
  
  <DIV style="margin-top: 6pt">
  <TABLE width="100%" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt">
  
  <TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="4%" style="background: transparent">&nbsp;</TD>
      <TD width="3%" nowrap align="left">(1)</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>To file, during any period in which offers or sales are being made, a post-effective
  amendment to this Registration Statement:</TD>
  </TR>
  
  </TABLE>
  </DIV>
  
  <DIV style="margin-top: 6pt">
  <TABLE width="100%" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt">
  
  <TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="8%" style="background: transparent">&nbsp;</TD>
      <TD width="3%" nowrap align="left">(i)</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>To include any prospectus required by Section&nbsp;10(a)(3) of the
  Securities Act of 1933, as amended (the &#147;Securities Act&#148;);</TD>
  </TR>
  
  </TABLE>
  </DIV>
  
  <DIV style="margin-top: 6pt">
  <TABLE width="100%" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt">
  
  <TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="8%" style="background: transparent">&nbsp;</TD>
      <TD width="3%" nowrap align="left">(ii)</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>To reflect in the prospectus any facts or events arising after
  the effective date of the Registration Statement (or the most recent
  post-effective amendment thereof) which, individually or in the aggregate,
  represent a fundamental change in the information set forth in the Registration
  Statement. Notwithstanding the foregoing, any increase or decrease in volume
  of securities offered (if the total dollar value of securities offered would
  not exceed that which was registered) and any deviation from the low or high
  end of the estimated maximum offering range may be reflected in the form of a
  prospectus filed with the Commission pursuant to Rule 424(b) if, in the
  aggregate, the changes in volume and price represent no more than 20&nbsp;percent
  change in the maximum aggregate offering price set forth in the &#147;Calculation of
  Registration Fee&#148; table in the effective registration statement;</TD>
  </TR>
  
  </TABLE>
  </DIV>
  
  <DIV style="margin-top: 6pt">
  <TABLE width="100%" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt">
  
  <TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="8%" style="background: transparent">&nbsp;</TD>
      <TD width="3%" nowrap align="left">(iii)</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>To include any material information with respect to the plan
  of distribution not previously disclosed in the Registration Statement or any
  material change to such information in the Registration Statement;</TD>
  </TR>
  
  </TABLE>
  </DIV>
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt"><I>provided, however</I>, that paragraphs (a)(1)(i) and (a)(1)(ii) above shall not apply if the
  information required to be included in a post-effective amendment by those paragraphs is contained
  in periodic reports filed with or furnished
  </DIV>
  <P align="center" style="font-size: 10pt"><!-- Folio -->&nbsp;<!-- /Folio -->
  </DIV>
  
  <!-- PAGEBREAK -->
  <P><HR noshade><P>
  <H5 align="left" style="page-break-before:always"><A HREF="#toc">Table of Contents</A></H5><P>
  
  <DIV style="font-family: 'Times New Roman',Times,serif">
  
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">to the Commission by the Registrant pursuant to Section&nbsp;13 or 15(d) of the Exchange Act that are
  incorporated by reference in the Registration Statement.
  </DIV>
  
  
  <DIV style="margin-top: 6pt">
  <TABLE width="100%" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt">
  
  <TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="4%" style="background: transparent">&nbsp;</TD>
      <TD width="3%" nowrap align="left">(2)</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>That, for the purpose of determining any liability under the Securities Act,
  each such post-effective amendment shall be deemed to be a new registration statement
  relating to the securities offered therein, and the offering of such securities at that
  time shall be deemed to be the initial bona fide offering thereof.</TD>
  </TR>
  
  </TABLE>
  </DIV>
  
  <DIV style="margin-top: 6pt">
  <TABLE width="100%" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt">
  
  <TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="4%" style="background: transparent">&nbsp;</TD>
      <TD width="3%" nowrap align="left">(3)</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>To remove from registration by means of a post-effective amendment any of the
  securities being registered which remain unsold at the termination of the offering.</TD>
  </TR>
  
  </TABLE>
  </DIV>
  
  <DIV style="margin-top: 6pt">
  <TABLE width="100%" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt">
  
  <TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="3%" nowrap align="left">(b)</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>The undersigned Registrant hereby undertakes that, for purposes of determining any liability
  under the Securities Act, each filing of the Registrant&#146;s annual report pursuant to Section
  13(a) or 15(d) of the Exchange Act (and, where applicable, each filing of an employee benefit
  plan&#146;s annual report pursuant to Section 15(d) of the Exchange Act) that is incorporated by
  reference in the Registration Statement shall be deemed to be a new Registration Statement
  relating to the securities offered therein, and the offering of such securities at that time
  shall be deemed to be the initial bona fide offering thereof.</TD>
  </TR>
  
  </TABLE>
  </DIV>
  
  <DIV style="margin-top: 6pt">
  <TABLE width="100%" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt">
  
  <TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="3%" nowrap align="left">(c)</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>Insofar as indemnification for liabilities arising under the Securities Act may be permitted
  to directors, officers and controlling persons of the Registrant pursuant to the foregoing
  provisions, or otherwise, the Registrant has been advised that in the opinion of the
  Commission such indemnification is against public policy as expressed in the Securities Act
  and is, therefore, unenforceable. In the event that a claim for indemnification against such
  liabilities (other than the payment by the Registrant of expenses incurred or paid by a
  director, officer or controlling person of the Registrant in the successful defense of any
  action, suit or proceeding) is asserted by such director, officer or controlling person in
  connection with the securities being registered, the Registrant will, unless in the opinion of
  its counsel the matter has been settled by controlling precedent, submit to a court of
  appropriate jurisdiction the question whether such indemnification by it is against public
  policy as expressed in the Securities Act and will be governed by the final adjudication of
  such issue.</TD>
  </TR>
  
  
  </TABLE>
  </DIV>
  <P align="center" style="font-size: 10pt"><!-- Folio -->&nbsp;<!-- /Folio -->
  </DIV>
  
  <!-- PAGEBREAK -->
  <P><HR noshade><P>
  <H5 align="left" style="page-break-before:always"><A HREF="#toc">Table of Contents</A></H5><P>
  
  <DIV style="font-family: 'Times New Roman',Times,serif">
  
  
  <!-- link1 "SIGNATURES" -->
  <DIV align="left"><A NAME="005"></A></DIV>
  
  <DIV align="center" style="font-size: 10pt; margin-top: 18pt"><B>SIGNATURES</B>
  </DIV>
  
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Pursuant to the requirements of the Securities Act of 1933, as amended, the Registrant
  certifies that it has reasonable grounds to believe that it meets all of the requirements for
  filing on Form S-8 and has duly caused this Registration Statement to be signed on its behalf by
  the undersigned, thereunto duly authorized, in the City of Worcester, Commonwealth of Massachusetts
  on October&nbsp;2, 2008.
  </DIV>
  
  <TABLE width="100%" border="0" cellspacing="0" cellpadding="0" style="font-size: 10pt">
  <TR>
      <TD width="48%">&nbsp;</TD>
      <TD width="1%">&nbsp;</TD>
      <TD width="1%">&nbsp;</TD>
      <TD width="35%">&nbsp;</TD>
      <TD width="15%">&nbsp;</TD>
  </TR>
  <TR>
      <TD valign="top" align="left">&nbsp;</TD>
      <TD colspan="3" align="left">RXi PHARMACEUTICALS CORPORATION<BR>
  &nbsp;</TD>
      <TD>&nbsp;</TD>
  </TR><TR>
      <TD align="left">&nbsp;</TD>
      <TD valign="top">By:&nbsp;&nbsp;</TD>
      <TD colspan="2" style="border-bottom: 1px solid #000000" align="left">/s/  Tod Woolf
  &nbsp;</TD>
      <TD>&nbsp;</TD>
  </TR><TR>
      <TD align="left">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD colspan="2" align="left">Tod Woolf, Ph.D.&nbsp;</TD>
      <TD>&nbsp;</TD>
  </TR><TR>
      <TD align="left">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD colspan="2" align="left">President and Chief Executive Officer&nbsp;</TD>
      <TD>&nbsp;</TD>
  </TR>
  <TR>
      <TD colspan="5">&nbsp;</TD>
  </TR>
  </TABLE>
  
  <DIV align="center" style="font-size: 10pt; margin-top: 12pt"><B>POWER OF ATTORNEY</B>
  </DIV>
  
  
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutes
  and appoints STEPHEN J. DIPALMA and TOD WOOLF, PH.D., and each of them, either of whom may act
  without the joinder of the other, as his true and lawful attorneys-in-fact and agents, with full
  power of substitution and resubstitution, for him and in his name, place, and stead, in any and all
  capacities, to sign any and all amendments (including post-effective amendments, exhibits thereto
  and other documents in connection therewith) to this Registration Statement, and to file the same,
  with all exhibits thereto, and other documents in connection therewith (including any registration
  statement relating to this Registration Statement and filed pursuant to Rule 462(b) of the
  Securities Act of 1933, as amended), with the Securities and Exchange Commission, granting unto
  said attorneys-in-fact and agents, and each of them, full power and authority to do and perform
  each and every act and thing requisite and necessary to be done in connection therewith, as fully
  to all intents and purposes as he might or could do in person, hereby ratifying and confirming all
  that said attorneys-in-fact and agents, or either of them, or their or his substitute or
  substitutes, may lawfully do or cause to be done by virtue hereof.
  </DIV>
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Pursuant to the requirements of the Securities Act of 1933, as amended, this Registration
  Statement has been signed below by the following persons in the capacities and on the dates
  indicated.
  </DIV>
  <DIV align="center">
  <TABLE style="font-size: 10pt" cellspacing="0" border="0" cellpadding="0" width="100%">
  <!-- Begin Table Head -->
  <TR valign="bottom">
      <TD width="29%">&nbsp;</TD>
      <TD width="3%">&nbsp;</TD>
      <TD width="42%">&nbsp;</TD>
      <TD width="3%">&nbsp;</TD>
      <TD width="23%">&nbsp;</TD>
  </TR>
  <TR style="font-size: 8pt" valign="bottom">
      <TD nowrap align="center">SIGNATURES</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center">TITLE</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center">DATE</TD>
  </TR>
  
  <!-- End Table Head -->
  <!-- Begin Table Body -->
  <TR valign="bottom"><!-- Blank Space -->
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
  </TR>
  <TR valign="bottom">
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">/s/ Tod Woolf
  <DIV style="font-size: 1pt; border-top: 1px solid #000000">&nbsp;</DIV>
  Tod Woolf, Ph.D.
  </DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">President and Chief Executive Officer<BR>
  (Principal Executive Officer)&nbsp;
  </TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">October&nbsp;2, 2008&nbsp;</TD>
  </TR>
  <TR valign="bottom"><!-- Blank Space -->
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
  </TR>
  <TR valign="bottom">
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">/s/ Stephen J. DiPalma
  <DIV style="font-size: 1pt; border-top: 1px solid #000000">&nbsp;</DIV>
  Stephen J. DiPalma
  </DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">Chief Financial Officer<br>
  (Principal Financial and Accounting
  Officer)
  </TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">October&nbsp;2, 2008&nbsp;</TD>
  </TR>
  <TR valign="bottom"><!-- Blank Space -->
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
  </TR>
  <TR valign="bottom">
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">/s/ Sanford J. Hillsberg
  <DIV style="font-size: 1pt; border-top: 1px solid #000000">&nbsp;</DIV>
  Sanford J. Hillsberg
  </DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">Director&nbsp;
  </TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">October&nbsp;2, 2008&nbsp;</TD>
  </TR>
  <TR valign="bottom"><!-- Blank Space -->
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
  </TR>
  <TR valign="bottom">
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">/s/ Mark J. Ahn
  <DIV style="font-size: 1pt; border-top: 1px solid #000000">&nbsp;</DIV>
  Mark J. Ahn
  </DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">Director&nbsp;
  </TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">October&nbsp;2, 2008&nbsp;</TD>
  </TR>
  <TR valign="bottom"><!-- Blank Space -->
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
  </TR>
  <TR valign="bottom">
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">/s/ Stephen S. Galliker
  <DIV style="font-size: 1pt; border-top: 1px solid #000000">&nbsp;</DIV>
  Stephen S. Galliker
  </DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">Director&nbsp;
  </TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">October&nbsp;2, 2008&nbsp;</TD>
  </TR>
  <TR valign="bottom"><!-- Blank Space -->
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
  </TR>
  <TR valign="bottom">
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">/s/ Steven A. Kriegsman
  <DIV style="font-size: 1pt; border-top: 1px solid #000000">&nbsp;</DIV>
  Steven A. Kriegsman
  </DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">Director&nbsp;
  </TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">October&nbsp;2, 2008&nbsp;</TD>
  </TR>
  <!-- End Table Body -->
  </TABLE>
  </DIV>
  
  
  <P align="center" style="font-size: 10pt"><!-- Folio -->&nbsp;<!-- /Folio -->
  </DIV>
  
  <!-- PAGEBREAK -->
  <P><HR noshade><P>
  <H5 align="left" style="page-break-before:always"><A HREF="#toc">Table of Contents</A></H5><P>
  
  <DIV style="font-family: 'Times New Roman',Times,serif">
  
  <!-- link1 "EXHIBIT INDEX" -->
  <DIV align="left"><A NAME="006"></A></DIV>
  
  <DIV align="left" style="font-size: 10pt; margin-top: 12pt"><B>EXHIBIT INDEX</B>
  </DIV>
  
  <DIV align="center">
  <TABLE style="font-size: 10pt" cellspacing="0" border="0" cellpadding="0" width="100%">
  <!-- Begin Table Head -->
  <TR valign="bottom">
      <TD width="6%">&nbsp;</TD>
      <TD width="2%">&nbsp;</TD>
      <TD width="92%">&nbsp;</TD>
  </TR>
  <!-- End Table Head -->
  <!-- Begin Table Body -->
  <TR valign="bottom">
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">4.1
  </DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">2007 Incentive Plan (previously filed as Exhibit&nbsp;10.19 to the Registration
  Statement on Form&nbsp;S-1, as amended, No.&nbsp;333-147009, and incorporated herein
  by reference).</TD>
  </TR>
  <TR valign="bottom"><!-- Blank Space -->
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
  </TR>
  <TR valign="bottom">
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">4.2
  </DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">Amended and Restated Certificate of Incorporation (previously filed as
  Exhibit&nbsp;3.1 to the Registration Statement on Form&nbsp;S-1, as amended, No.
  333-147009, and incorporated herein by reference).</TD>
  </TR>
  <TR valign="bottom"><!-- Blank Space -->
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
  </TR>
  <TR valign="bottom">
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">4.3
  </DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">Amended and Restated Bylaws, as amended (previously filed as Exhibit&nbsp;3.2 to
  the Registration Statement on Form&nbsp;S-1, as amended, No.&nbsp;333-147009, and
  incorporated herein by reference).</TD>
  </TR>
  <TR valign="bottom"><!-- Blank Space -->
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
  </TR>
  <TR valign="bottom">
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">5.1
  </DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">Opinion of Ropes &#038; Gray LLP.</TD>
  </TR>
  <TR valign="bottom"><!-- Blank Space -->
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
  </TR>
  <TR valign="bottom">
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">23.1
  </DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">Consent of BDO Seidman, LLP, Independent Registered Public Accounting Firm.</TD>
  </TR>
  <TR valign="bottom"><!-- Blank Space -->
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
  </TR>
  <TR valign="bottom">
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">23.2
  </DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">Consent of Ropes &#038; Gray, LLP (see Exhibit&nbsp;5.1).</TD>
  </TR>
  <TR valign="bottom"><!-- Blank Space -->
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
  </TR>
  <TR valign="bottom">
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">24.1
  </DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">Power of Attorney (included on the signature page hereto).</TD>
  </TR>
  <!-- End Table Body -->
  </TABLE>
  </DIV>
  
  
  
  <P align="center" style="font-size: 10pt"><!-- Folio -->&nbsp;<!-- /Folio -->
  </DIV>
  
  
  
  
  </BODY>
  </HTML>
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text: sv8
  Table of Contents
  As filed with the Securities and Exchange Commission on
  October 3, 2008
  Registration No. 333-
  UNITED STATES
  SECURITIES AND EXCHANGE COMMISSION
  Washington, D.C. 20549
  FORM S-8
  REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933
  RXi PHARMACEUTICALS CORPORATION
  (Exact name of registrant as specified in its charter)
  Delaware
  20-8099512
  (State or other jurisdiction
  of incorporation or organization)
  (I.R.S Employer Identification No.)
  60 Prescott Street, Worcester, Massachusetts
  01605
  (Address of Principal Executive Offices)
  (Zip Code)
  RXi Pharmaceuticals Corporation 2007 Incentive Plan
  (Full title of the plan)
  Tod Woolf, Ph.D.
  Chief Executive Officer
  RXi Pharmaceuticals Corporation
  60 Prescott Street
  Worcester, Massachusetts 01605
  (508) 767-3861
  With copies to:
  Marc A. Rubenstein, Esq.
  Ropes & Gray LLP
  One International Place
  Boston, Massachusetts 02110
  (617) 951-7000
  (Name, address, and telephone number, including area code, of agent for service)
  Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer or a smaller reporting company. See the definitions of "large accelerated filer," "accelerated filer" and "smaller reporting company" in Rule 12b-2 of the Exchange Act. (Check one):
  Large accelerated filer
  o
  Accelerated filer
  o
  Non-accelerated filer
  o
  (Do not check if a smaller reporting company)
  Smaller reporting company
  þ
  CALCULATION OF REGISTRATION FEE
  Proposed maximum
  Title of each class of
  Amount to be
  offering price
  Proposed maximum
  Amount of
  securities to be registered
  registered (1)
  per share (2)
  aggregate offering price
  registration fee
  Common Stock,
  $.0001 par value
  per share
  1,000,000
  $
  8.00
  $
  8,000,000
  $314
  (1)
  Pursuant to Rule 416(a) under the Securities Act of 1933, this registration statement also
  covers such additional shares as may be required pursuant to RXi Pharmaceuticals Corporation's 2007
  Incentive Plan in the event of a stock dividend, stock split, recapitalization or other similar
  change in the common stock.
  (2)
  The offering price of $8.00 per share has been estimated solely for the purpose of determining
  the registration fee pursuant to Rule 457(c) and 457(h)(1) on the basis of the average high and low
  prices of the Common Stock, as reported on the Nasdaq Capital Market on September 29, 2008.
  TABLE OF CONTENTS
  ITEM 5. Interest of Named Experts and Counsel.
  ITEM 6. Indemnification of Directors and Officers.
  ITEM 7. Exemption from Registration Claimed.
  ITEM 8. Exhibits.
  ITEM 9. Undertakings.
  SIGNATURES
  EXHIBIT INDEX
  EX-5.1 Opinion of Ropes & Gray LLP
  EX-23.1 Consent of BDO Seidman, LLP, Independent Registered Public Accounting Firm.
  Table of Contents
  EXPLANATORY NOTE
  This Registration Statement is being filed to increase the number of shares of common stock,
  par value $.0001 per share, of RXi Pharmaceuticals Corporation that may be issued and sold pursuant
  to the RXi Pharmaceuticals Corporation's 2007 Incentive Plan by an additional 1,000,000 shares.
  Pursuant to Instruction E to Form S-8, the Registrant incorporates by reference into this
  Registration Statement the entire contents of its Registration Statement on Form S-8 (File No.
  333-151154) filed with the Securities and Exchange Commission on May 23, 2008, except with respect
  to Items 5, 6, 7, 8 and 9.
  ITEM 5. Interest of Named Experts and Counsel.
  Not applicable.
  ITEM 6. Indemnification of Directors and Officers.
  Section 145 of the Delaware General Corporation Law provides that a corporation may indemnify
  any person who was or is a party or is threatened to be made a party to any threatened, pending or
  completed action, suit or proceeding, whether civil, criminal, administrative or investigative,
  other than an action by or in the right of the corporation, by reason of the fact that the person
  is or was a director, officer, employee or agent of the corporation or is or was serving at the
  corporation's request as a director, officer, employee or agent of another corporation,
  partnership, joint venture, trust or other enterprise, against expenses, including attorneys' fees,
  judgments, fines and amounts paid in settlement actually and reasonably incurred by the person in
  connection with the action, suit or proceeding if the person acted in good faith and in a manner
  the person reasonably believed to be in or not opposed to the best interests of the corporation,
  and, with respect to any criminal action or proceeding, had no reasonable cause to believe the
  person's conduct was unlawful. The power to indemnify applies to actions brought by or in the right
  of the corporation as well, but only to the extent of expenses, including attorneys' fees but
  excluding judgments, fines and amounts paid in settlement, actually and reasonably incurred by the
  person in connection with the defense or settlement of the action or suit if the person acted in
  good faith and in a manner the person reasonably believed to be in or not opposed to the best
  interests of the corporation and except that no indemnification shall be made in respect of any
  claim, issue or matter as to which such person shall have been adjudged to be liable to the
  corporation unless and only to the extent that a court of competent jurisdiction shall determine
  that such indemnity is proper.
  Section 145(g) of the Delaware General Corporation Law provides that a corporation shall have
  the power to purchase and maintain insurance on behalf of its officers, directors, employees and
  agents, against any liability asserted against and incurred by such persons in any such capacity.
  Section 102(b)(7) of the General Corporation Law of the State of Delaware provides that a
  corporation may eliminate or limit the personal liability of a director to the corporation or its
  stockholders for monetary damages for breach of fiduciary duty as a director, provided that such
  provision shall not eliminate or limit the liability of a director (i) for any breach of the
  director's duty of loyalty to the corporation or its stockholders, (ii) for acts or omissions not
  in good faith or which involve intentional misconduct or a knowing violation of law, (iii) under
  Section 174 of the General Corporation Law of the State of Delaware, or (iv) for any transaction
  from which the director derived an improper personal benefit. No such provision shall eliminate or
  limit the liability of a director for any act or omission occurring prior to the date when such
  provision becomes effective.
  Our Amended and Restated Certificate of Incorporation provides that our directors shall not be
  liable to the Registrant or its stockholders for monetary damages for breach of fiduciary duty as a
  director, except to the extent that the exculpation from liabilities is not permitted under the
  Delaware General Corporation Law as in effect at the time such liability is determined. In
  addition, our Amended and Restated Certificate of Incorporation provides that we shall indemnify
  our directors to the fullest extent permitted by the laws of the State of Delaware. We have entered
  into indemnification agreements with each of our non-employee directors that provide for
  indemnification and expense advancement to the fullest extent permitted by the laws of the State of
  Delaware.
  Our Amended and Restated Certificate of Incorporation provides that we may purchase and
  maintain insurance policies on behalf of our directors and officers against specified liabilities
  for actions taken in their
  Table of Contents
  capacities as such, including liabilities under the Securities Act. We have obtained directors and
  officers' liability insurance to cover liabilities our directors and officers may incur in
  connection with their services to the Registrant.
  ITEM 7. Exemption from Registration Claimed.
  Not applicable.
  ITEM 8. Exhibits.
  4.1
  2007 Incentive Plan (previously filed as Exhibit 10.19 to the Registration
  Statement on Form S-1, as amended, No. 333-147009, and incorporated herein by
  reference).
  4.2
  Amended and Restated Certificate of Incorporation (previously filed as
  Exhibit 3.1 to the Registration Statement on Form S-1, as amended, No.
  333-147009, and incorporated herein by reference).
  4.3
  Amended and Restated Bylaws, as amended (previously filed as Exhibit 3.2 to
  the Registration Statement on Form S-1, as amended, No. 333-147009, and
  incorporated herein by reference).
  5.1
  Opinion of Ropes & Gray LLP.
  23.1
  Consent of BDO Seidman, LLP, Independent Registered Public Accounting Firm.
  23.2
  Consent of Ropes & Gray, LLP (see Exhibit 5.1).
  24.1
  Power of Attorney (included on the signature page hereto).
  ITEM 9. Undertakings.
  (a)
  The undersigned Registrant hereby undertakes:
  (1)
  To file, during any period in which offers or sales are being made, a post-effective
  amendment to this Registration Statement:
  (i)
  To include any prospectus required by Section 10(a)(3) of the
  Securities Act of 1933, as amended (the "Securities Act");
  (ii)
  To reflect in the prospectus any facts or events arising after
  the effective date of the Registration Statement (or the most recent
  post-effective amendment thereof) which, individually or in the aggregate,
  represent a fundamental change in the information set forth in the Registration
  Statement. Notwithstanding the foregoing, any increase or decrease in volume
  of securities offered (if the total dollar value of securities offered would
  not exceed that which was registered) and any deviation from the low or high
  end of the estimated maximum offering range may be reflected in the form of a
  prospectus filed with the Commission pursuant to Rule 424(b) if, in the
  aggregate, the changes in volume and price represent no more than 20 percent
  change in the maximum aggregate offering price set forth in the "Calculation of
  Registration Fee" table in the effective registration statement;
  (iii)
  To include any material information with respect to the plan
  of distribution not previously disclosed in the Registration Statement or any
  material change to such information in the Registration Statement;
  provided, however
  , that paragraphs (a)(1)(i) and (a)(1)(ii) above shall not apply if the
  information required to be included in a post-effective amendment by those paragraphs is contained
  in periodic reports filed with or furnished
  Table of Contents
  to the Commission by the Registrant pursuant to Section 13 or 15(d) of the Exchange Act that are
  incorporated by reference in the Registration Statement.
  (2)
  That, for the purpose of determining any liability under the Securities Act,
  each such post-effective amendment shall be deemed to be a new registration statement
  relating to the securities offered therein, and the offering of such securities at that
  time shall be deemed to be the initial bona fide offering thereof.
  (3)
  To remove from registration by means of a post-effective amendment any of the
  securities being registered which remain unsold at the termination of the offering.
  (b)
  The undersigned Registrant hereby undertakes that, for purposes of determining any liability
  under the Securities Act, each filing of the Registrant's annual report pursuant to Section
  13(a) or 15(d) of the Exchange Act (and, where applicable, each filing of an employee benefit
  plan's annual report pursuant to Section 15(d) of the Exchange Act) that is incorporated by
  reference in the Registration Statement shall be deemed to be a new Registration Statement
  relating to the securities offered therein, and the offering of such securities at that time
  shall be deemed to be the initial bona fide offering thereof.
  (c)
  Insofar as indemnification for liabilities arising under the Securities Act may be permitted
  to directors, officers and controlling persons of the Registrant pursuant to the foregoing
  provisions, or otherwise, the Registrant has been advised that in the opinion of the
  Commission such indemnification is against public policy as expressed in the Securities Act
  and is, therefore, unenforceable. In the event that a claim for indemnification against such
  liabilities (other than the payment by the Registrant of expenses incurred or paid by a
  director, officer or controlling person of the Registrant in the successful defense of any
  action, suit or proceeding) is asserted by such director, officer or controlling person in
  connection with the securities being registered, the Registrant will, unless in the opinion of
  its counsel the matter has been settled by controlling precedent, submit to a court of
  appropriate jurisdiction the question whether such indemnification by it is against public
  policy as expressed in the Securities Act and will be governed by the final adjudication of
  such issue.
  Table of Contents
  SIGNATURES
  Pursuant to the requirements of the Securities Act of 1933, as amended, the Registrant
  certifies that it has reasonable grounds to believe that it meets all of the requirements for
  filing on Form S-8 and has duly caused this Registration Statement to be signed on its behalf by
  the undersigned, thereunto duly authorized, in the City of Worcester, Commonwealth of Massachusetts
  on October 2, 2008.
  RXi PHARMACEUTICALS CORPORATION
  By:
  /s/  Tod Woolf
  Tod Woolf, Ph.D.
  President and Chief Executive Officer
  POWER OF ATTORNEY
  KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutes
  and appoints STEPHEN J. DIPALMA and TOD WOOLF, PH.D., and each of them, either of whom may act
  without the joinder of the other, as his true and lawful attorneys-in-fact and agents, with full
  power of substitution and resubstitution, for him and in his name, place, and stead, in any and all
  capacities, to sign any and all amendments (including post-effective amendments, exhibits thereto
  and other documents in connection therewith) to this Registration Statement, and to file the same,
  with all exhibits thereto, and other documents in connection therewith (including any registration
  statement relating to this Registration Statement and filed pursuant to Rule 462(b) of the
  Securities Act of 1933, as amended), with the Securities and Exchange Commission, granting unto
  said attorneys-in-fact and agents, and each of them, full power and authority to do and perform
  each and every act and thing requisite and necessary to be done in connection therewith, as fully
  to all intents and purposes as he might or could do in person, hereby ratifying and confirming all
  that said attorneys-in-fact and agents, or either of them, or their or his substitute or
  substitutes, may lawfully do or cause to be done by virtue hereof.
  Pursuant to the requirements of the Securities Act of 1933, as amended, this Registration
  Statement has been signed below by the following persons in the capacities and on the dates
  indicated.
  SIGNATURES
  TITLE
  DATE
  /s/ Tod Woolf
  Tod Woolf, Ph.D.
  President and Chief Executive Officer
  (Principal Executive Officer)
  October 2, 2008
  /s/ Stephen J. DiPalma
  Stephen J. DiPalma
  Chief Financial Officer
  (Principal Financial and Accounting
  Officer)
  October 2, 2008
  /s/ Sanford J. Hillsberg
  Sanford J. Hillsberg
  Director
  October 2, 2008
  /s/ Mark J. Ahn
  Mark J. Ahn
  Director
  October 2, 2008
  /s/ Stephen S. Galliker
  Stephen S. Galliker
  Director
  October 2, 2008
  /s/ Steven A. Kriegsman
  Steven A. Kriegsman
  Director
  October 2, 2008
  Table of Contents
  EXHIBIT INDEX
  4.1
  2007 Incentive Plan (previously filed as Exhibit 10.19 to the Registration
  Statement on Form S-1, as amended, No. 333-147009, and incorporated herein
  by reference).
  4.2
  Amended and Restated Certificate of Incorporation (previously filed as
  Exhibit 3.1 to the Registration Statement on Form S-1, as amended, No.
  333-147009, and incorporated herein by reference).
  4.3
  Amended and Restated Bylaws, as amended (previously filed as Exhibit 3.2 to
  the Registration Statement on Form S-1, as amended, No. 333-147009, and
  incorporated herein by reference).
  5.1
  Opinion of Ropes & Gray LLP.
  23.1
  Consent of BDO Seidman, LLP, Independent Registered Public Accounting Firm.
  23.2
  Consent of Ropes & Gray, LLP (see Exhibit 5.1).
  24.1
  Power of Attorney (included on the signature page hereto).