<?xml version="1.0" encoding="us-ascii"?><InstanceReport xmlns:xsd="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"><Version>2.4.0.8</Version><ReportLongName>2103100 - Disclosure - Stock-Based Compensation</ReportLongName><DisplayLabelColumn>true</DisplayLabelColumn><ShowElementNames>false</ShowElementNames><RoundingOption /><HasEmbeddedReports>false</HasEmbeddedReports><Columns><Column FlagID="0"><Id>1</Id><IsAbstractGroupTitle>false</IsAbstractGroupTitle><LabelSeparator>

</LabelSeparator><CurrencyCode /><FootnoteIndexer /><hasSegments>false</hasSegments><hasScenarios>false</hasScenarios><MCU><KeyName /><CurrencySymbol /><contextRef><ContextID>D2013Q2YTD</ContextID><EntitySchema>http://www.sec.gov/CIK</EntitySchema><EntityValue>0001113481</EntityValue><PeriodDisplayName /><PeriodType>duration</PeriodType><PeriodStartDate>2013-01-01T00:00:00</PeriodStartDate><PeriodEndDate>2013-06-30T00:00:00</PeriodEndDate><Segments /><Scenarios /></contextRef><UPS /><CurrencyCode /><OriginalCurrencyCode /></MCU><CurrencySymbol /><Labels><Label Key="CalendarSupplement" Id="0" Label="6 Months Ended" /><Label Key="Calendar" Id="1" Label="Jun. 30, 2013" /></Labels></Column></Columns><Rows><Row FlagID="0"><Id>1</Id><IsAbstractGroupTitle>true</IsAbstractGroupTitle><LabelSeparator>

</LabelSeparator><Level>1</Level><ElementName>us-gaap_DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract</ElementName><ElementPrefix>us-gaap_</ElementPrefix><IsBaseElement>true</IsBaseElement><BalanceType>na</BalanceType><PeriodType>duration</PeriodType><IsReportTitle>false</IsReportTitle><IsSegmentTitle>false</IsSegmentTitle><IsCalendarTitle>false</IsCalendarTitle><IsEquityPrevioslyReportedAsRow>false</IsEquityPrevioslyReportedAsRow><IsEquityAdjustmentRow>false</IsEquityAdjustmentRow><IsBeginningBalance>false</IsBeginningBalance><IsEndingBalance>false</IsEndingBalance><IsReverseSign>false</IsReverseSign><FootnoteIndexer /><Cells><Cell FlagID="0" ContextID="" UnitID=""><Id>1</Id><IsNumeric>false</IsNumeric><IsRatio>false</IsRatio><DisplayZeroAsNone>false</DisplayZeroAsNone><NumericAmount>0</NumericAmount><RoundedNumericAmount>0</RoundedNumericAmount><NonNumbericText /><FootnoteIndexer /><CurrencyCode /><CurrencySymbol /><IsIndependantCurrency>false</IsIndependantCurrency><ShowCurrencySymbol>false</ShowCurrencySymbol><DisplayDateInUSFormat>false</DisplayDateInUSFormat></Cell></Cells><ElementDataType>xbrli:stringItemType</ElementDataType><SimpleDataType>string</SimpleDataType><IsTotalLabel>false</IsTotalLabel><UnitID>0</UnitID><Label>Disclosure of Compensation Related Costs, Share-based Payments [Abstract]</Label></Row><Row FlagID="0"><Id>2</Id><IsAbstractGroupTitle>false</IsAbstractGroupTitle><LabelSeparator>

</LabelSeparator><Level>2</Level><ElementName>us-gaap_DisclosureOfCompensationRelatedCostsShareBasedPaymentsTextBlock</ElementName><ElementPrefix>us-gaap_</ElementPrefix><IsBaseElement>true</IsBaseElement><BalanceType>na</BalanceType><PeriodType>duration</PeriodType><IsReportTitle>false</IsReportTitle><IsSegmentTitle>false</IsSegmentTitle><IsCalendarTitle>false</IsCalendarTitle><IsEquityPrevioslyReportedAsRow>false</IsEquityPrevioslyReportedAsRow><IsEquityAdjustmentRow>false</IsEquityAdjustmentRow><IsBeginningBalance>false</IsBeginningBalance><IsEndingBalance>false</IsEndingBalance><IsReverseSign>false</IsReverseSign><PreferredLabelRole>verboseLabel</PreferredLabelRole><FootnoteIndexer /><Cells><Cell FlagID="0" ContextID="D2013Q2YTD" UnitID=""><Id>1</Id><IsNumeric>false</IsNumeric><IsRatio>false</IsRatio><DisplayZeroAsNone>false</DisplayZeroAsNone><NumericAmount>0</NumericAmount><RoundedNumericAmount>0</RoundedNumericAmount><NonNumbericText>&lt;div style="font-family:Times New Roman;font-size:10pt;"&gt;&lt;div style="line-height:120%;text-align:left;text-indent:18px;font-size:10pt;"&gt;&lt;font style="font-family:inherit;font-size:10pt;font-weight:bold;"&gt; Stock-Based Compensation&lt;/font&gt;&lt;/div&gt;&lt;div style="line-height:120%;text-align:left;padding-left:18px;font-size:10pt;"&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt;&lt;br clear="none"/&gt;&lt;/font&gt;&lt;/div&gt;&lt;div style="line-height:120%;text-align:justify;text-indent:18px;font-size:10pt;"&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt;The Company recorded approximately &lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;color:#000000;text-decoration:none;"&gt;$5.8 million&lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt; and &lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;color:#000000;text-decoration:none;"&gt;$10.5 million&lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt; of stock-based compensation expense for the &lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;color:#000000;text-decoration:none;"&gt;three and six&lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt; months ended &lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;color:#000000;text-decoration:none;"&gt;June&amp;#160;30, 2013&lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt;, respectively.  The Company recorded approximately &lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;color:#000000;text-decoration:none;"&gt;$4.2 million&lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt; and &lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;color:#000000;text-decoration:none;"&gt;$7.3 million&lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt; of stock-based compensation expense for the &lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;color:#000000;text-decoration:none;"&gt;three and six&lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt; months ended &lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;color:#000000;text-decoration:none;"&gt;June&amp;#160;30, 2012&lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt;, respectively.  As of &lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;color:#000000;text-decoration:none;"&gt;June&amp;#160;30, 2013&lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt;, there was approximately &lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;color:#000000;text-decoration:none;"&gt;$24.8 million&lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt; of total unrecognized compensation costs related to non-vested stock-based employee compensation arrangements granted under the Company's equity compensation plans. The Company expects to recognize those costs over a weighted average period of &lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;color:#000000;text-decoration:none;"&gt;1.38&lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt; years.&lt;/font&gt;&lt;/div&gt;&lt;div style="line-height:120%;text-align:left;font-size:10pt;"&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt;&lt;br clear="none"/&gt;&lt;/font&gt;&lt;/div&gt;&lt;div style="line-height:120%;text-align:justify;text-indent:18px;font-size:10pt;"&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt;During the &lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;color:#000000;text-decoration:none;"&gt;six&lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt; months ended &lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;color:#000000;text-decoration:none;"&gt;June&amp;#160;30, 2013&lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt;, the Company issued a total of &lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;color:#000000;text-decoration:none;"&gt;2,644,622&lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt; shares of its common stock upon the exercise of stock options, pursuant to restricted stock grants and pursuant to purchases under the 2010 ESPP. During the &lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;color:#000000;text-decoration:none;"&gt;six&lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt; months ended &lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;color:#000000;text-decoration:none;"&gt;June&amp;#160;30, 2012&lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt;, the Company issued a total of &lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;color:#000000;text-decoration:none;"&gt;973,056&lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt; shares of its common stock upon the exercise of stock options, pursuant to restricted stock grants and pursuant to purchases under the 2010 ESPP. Cash received from the exercise of stock options and purchases through the 2010 ESPP during the &lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;color:#000000;text-decoration:none;"&gt;six&lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt; months ended &lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;color:#000000;text-decoration:none;"&gt;June&amp;#160;30, 2013&lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt; and &lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;color:#000000;text-decoration:none;"&gt;June&amp;#160;30, 2012&lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt; was approximately &lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;color:#000000;text-decoration:none;"&gt;$49.6 million&lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt; and &lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;color:#000000;text-decoration:none;"&gt;$4.7 million&lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt;, respectively, and is included within the financing activities section of the consolidated statements of cash flows.&lt;/font&gt;&lt;/div&gt;&lt;div style="line-height:120%;text-align:left;font-size:10pt;"&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt;&lt;br clear="none"/&gt;&lt;/font&gt;&lt;/div&gt;&lt;div style="line-height:120%;text-align:justify;text-indent:18px;font-size:10pt;"&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt;At &lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;color:#000000;text-decoration:none;"&gt;June&amp;#160;30, 2013&lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt;, there were an aggregate of &lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;color:#000000;text-decoration:none;"&gt;4,793,759&lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt; shares of common stock reserved for future issuance under the 2010 ESPP and for future grants under the Company's &lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;color:#000000;text-decoration:none;"&gt;2013&lt;/font&gt;&lt;font style="font-family:inherit;font-size:10pt;"&gt; stock incentive plan.&lt;/font&gt;&lt;/div&gt;&lt;/div&gt;</NonNumbericText><FootnoteIndexer /><CurrencyCode /><CurrencySymbol /><IsIndependantCurrency>false</IsIndependantCurrency><ShowCurrencySymbol>false</ShowCurrencySymbol><DisplayDateInUSFormat>false</DisplayDateInUSFormat></Cell></Cells><ElementDataType>nonnum:textBlockItemType</ElementDataType><SimpleDataType>na</SimpleDataType><ElementDefenition>The entire disclosure for compensation-related costs for equity-based compensation, which may include disclosure of policies, compensation plan details, allocation of equity compensation, incentive distributions, equity-based arrangements to obtain goods and services, deferred compensation arrangements, employee stock ownership plan details and employee stock purchase plan details.</ElementDefenition><ElementReferences>Reference 1: http://www.xbrl.org/2003/role/presentationRef

 -Publisher FASB

 -Name Accounting Standards Codification

 -Topic 718

 -SubTopic 10

 -Section 50

 -Paragraph 1

 -URI http://asc.fasb.org/extlink&amp;oid=6415400&amp;loc=d3e5047-113901



Reference 2: http://www.xbrl.org/2003/role/presentationRef

 -Publisher FASB

 -Name Accounting Standards Codification

 -Topic 718

 -SubTopic 10

 -Section 50

 -Paragraph 2

 -URI http://asc.fasb.org/extlink&amp;oid=6415400&amp;loc=d3e5070-113901



Reference 3: http://www.xbrl.org/2003/role/presentationRef

 -Publisher FASB

 -Name Accounting Standards Codification

 -Topic 505

 -SubTopic 50

 -Section 50

 -Paragraph 1

 -URI http://asc.fasb.org/extlink&amp;oid=6406099&amp;loc=d3e25284-112666



Reference 4: http://www.xbrl.org/2003/role/presentationRef

 -Publisher FASB

 -Name Accounting Standards Codification

 -Topic 718

 -SubTopic 40

 -Section 50

 -Paragraph 1

 -URI http://asc.fasb.org/extlink&amp;oid=6418621&amp;loc=d3e17540-113929



Reference 5: http://www.xbrl.org/2003/role/presentationRef

 -Publisher FASB

 -Name Accounting Standards Codification

 -Topic 718

 -SubTopic 10

 -Section 50

 -Paragraph 4

 -URI http://asc.fasb.org/extlink&amp;oid=6415400&amp;loc=d3e5444-113901



Reference 6: http://www.xbrl.org/2003/role/presentationRef

 -Publisher SEC

 -Name Staff Accounting Bulletin (SAB)

 -Number Topic 14



</ElementReferences><IsTotalLabel>false</IsTotalLabel><UnitID>0</UnitID><Label>Stock-Based Compensation</Label></Row></Rows><Footnotes /><IsEquityReport>false</IsEquityReport><ReportName>Stock-Based Compensation</ReportName><MonetaryRoundingLevel>UnKnown</MonetaryRoundingLevel><SharesRoundingLevel>UnKnown</SharesRoundingLevel><PerShareRoundingLevel>UnKnown</PerShareRoundingLevel><ExchangeRateRoundingLevel>UnKnown</ExchangeRateRoundingLevel><HasCustomUnits>true</HasCustomUnits><IsEmbedReport>false</IsEmbedReport><IsMultiCurrency>false</IsMultiCurrency><ReportType>Sheet</ReportType><RoleURI>http://www.themedicinescompany.com/role/StockBasedCompensation</RoleURI><NumberOfCols>1</NumberOfCols><NumberOfRows>2</NumberOfRows></InstanceReport>
