<?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>107 - Disclosure - Organization, Basis of Presentation and Significant Accounting Policies</ReportLongName><DisplayLabelColumn>true</DisplayLabelColumn><ShowElementNames>false</ShowElementNames><RoundingOption /><HasEmbeddedReports>false</HasEmbeddedReports><Columns><Column FlagID="0"><Id>1</Id><IsAbstractGroupTitle>false</IsAbstractGroupTitle><LabelSeparator>

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</LabelSeparator><Level>2</Level><ElementName>us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock</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="P01_01_2013To06_30_2013" UnitID=""><Id>1</Id><IsNumeric>false</IsNumeric><IsRatio>false</IsRatio><DisplayZeroAsNone>false</DisplayZeroAsNone><NumericAmount>0</NumericAmount><RoundedNumericAmount>0</RoundedNumericAmount><NonNumbericText>              &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt;MARGIN: 0pt 0px; FONT: 10pt Times New Roman, Times, Serif "&gt;  &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt;TEXT-INDENT: 0in; MARGIN: 0pt 0px; FONT: bold 10pt Times New Roman, Times, Serif"   align="justify"&gt;Note 1. Organization, Basis of Presentation and  Significant Accounting Policies&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt;TEXT-INDENT: 0in; MARGIN: 0pt 0px; FONT: bold 10pt Times New Roman, Times, Serif"   align="justify"&gt;&amp;#160;&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt;TEXT-INDENT: 0.5in; MARGIN: 0pt 0px; FONT: 10pt Times New Roman, Times, Serif"   align="justify"&gt;The accompanying unaudited interim consolidated  financial statements of Vertical Computer Systems, Inc.  (&amp;#8216;we&amp;#8221;, &amp;#8220;our&amp;#8221;, the &amp;#8220;Company&amp;#8221; or  &amp;#8220;Vertical&amp;#8221;) have been prepared in accordance with  accounting principles generally accepted in the United States of  America and rules&amp;#160;of the Securities and Exchange Commission,  and should be read in conjunction with the audited consolidated  financial statements and notes thereto contained in  Vertical&amp;#8217;s annual report on Form 10-K for the year ended  December 31, 2012. The consolidated financial statements include  the accounts of the Company and its subsidiaries (collectively,  &amp;#8220;our&amp;#8221;, &amp;#8220;we&amp;#8221;, the &amp;#8220;Company&amp;#8221; or  &amp;#8220;VCSY&amp;#8221;, as applicable). NOW Solutions, a wholly-owned  subsidiary of Vertical currently maintains daily business  operations, EnFacet, Inc. (&amp;#8220;ENF&amp;#8221;), Globalfare.com, Inc.  (&amp;#8220;GFI&amp;#8221;), Pointmail.com, Inc. (&amp;#8220;PMI&amp;#8221;) and  Vertical Internet Solutions, Inc. (&amp;#8220;VIS&amp;#8221;), each of  which is a wholly-owned subsidiary and is inactive and Vertical  Healthcare Solutions, Inc. (&amp;#8220;VHS&amp;#8221;), SnAPPnet, Inc.  (&amp;#8220;SnAPPnet&amp;#8221;), OptVision Research, Inc.  (&amp;#8220;OVR&amp;#8221;), Taladin, Inc. (&amp;#8220;Taladin&amp;#8221;), and  Vertical do Brasil, each of which has minor activities, are all  wholly-owned subsidiaries of Vertical. Government Internet Systems,  Inc. (&amp;#8220;GIS&amp;#8221;), an &lt;font style=" FONT-SIZE: 10pt"&gt;  84.5&lt;/font&gt;% owned subsidiary, and Priority Time Systems, Inc.  (&amp;#8220;Priority Time&amp;#8221;), a &lt;font style=" FONT-SIZE: 10pt"&gt;  90&lt;/font&gt;% owned subsidiary, are entities with minor activities. In  the opinion of management, all adjustments, consisting of normal  recurring adjustments, necessary for a fair presentation of  financial position and the results of operations for the interim  periods presented have been reflected herein. The results of  operations for interim periods are not necessarily indicative of  the results to be expected for the full year. Notes to the  consolidated financial statements which would substantially  duplicate the disclosure contained in the audited financial  statements as reported in the 2012 annual report on Form 10-K have  been omitted.&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt;MARGIN: 0pt 0px; FONT: 10pt Times New Roman, Times, Serif"   align="justify"&gt;&amp;#160;&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt"&gt;&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt"&gt;&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt"&gt;&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt;MARGIN: 0pt 0px; FONT: 10pt Times New Roman, Times, Serif"   align="justify"&gt;&lt;b&gt;&lt;i&gt;Earnings per share&lt;/i&gt;&lt;/b&gt;&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt;MARGIN: 0pt 0px; FONT: 10pt Times New Roman, Times, Serif"   align="justify"&gt;&lt;b&gt;&lt;i&gt;&amp;#160;&lt;/i&gt;&lt;/b&gt;&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt;TEXT-INDENT: 0.5in; MARGIN: 0pt 0px; FONT: 10pt Times New Roman, Times, Serif"   align="justify"&gt;Basic earnings per share is calculated by dividing  net income (loss) available to common stockholders by the weighted  average number of shares of the Company&amp;#8217;s common stock  outstanding during the period. &amp;#8220;Diluted earnings per  share&amp;#8221; reflects the potential dilution that could occur if  our share-based awards and convertible securities were exercised or  converted into common stock. The dilutive effect of our share-based  awards is computed using the treasury stock method, which assumes  all share-based awards are exercised and the hypothetical proceeds  from exercise are used to purchase common stock at the average  market price during the period. The incremental shares (difference  between shares assumed to be issued versus purchased), to the  extent they would have been dilutive, are included in the  denominator of the diluted EPS calculation. The dilutive effect of  our convertible preferred stock and convertible debentures is  computed using the if-converted method, which assumes conversion at  the beginning of the year.&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt"&gt;&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt;MARGIN: 0pt 0px; FONT: 10pt Times New Roman, Times, Serif"   align="justify"&gt;&amp;#160;&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt;TEXT-INDENT: 0.5in; MARGIN: 0pt 0px; FONT: 10pt Times New Roman, Times, Serif"   align="justify"&gt;For the six months ended June 30, 2013 and 2012,  common stock equivalents related to the convertible debentures,  convertible debt and preferred stock and stock derivative liability  were not included in the calculation of the diluted earnings per  share as their effect would be anti-dilutive.&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt"&gt;&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt"&gt;&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt;TEXT-INDENT: 0.5in; MARGIN: 0pt 0px; FONT: 10pt Times New Roman, Times, Serif"   align="justify"&gt;&amp;#160;&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt"&gt;&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt"&gt;&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt;MARGIN: 0pt 0px; FONT: 10pt Times New Roman, Times, Serif"   align="justify"&gt;&lt;b&gt;&lt;i&gt;Reclassifications&lt;/i&gt;&lt;/b&gt;&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt;MARGIN: 0pt 0px; FONT: 10pt Times New Roman, Times, Serif"   align="justify"&gt;&amp;#160;&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt;TEXT-INDENT: 0.5in; MARGIN: 0pt 0px; FONT: 10pt Times New Roman, Times, Serif"   align="justify"&gt;Certain reclassifications have been made to the  prior periods to conform to the current period presentation.&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt"&gt;&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt"&gt;&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt;TEXT-INDENT: 0.5in; MARGIN: 0pt 0px; FONT: 10pt Times New Roman, Times, Serif"   align="justify"&gt;&amp;#160;&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt"&gt;&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt"&gt;&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt;TEXT-INDENT: 0in; MARGIN: 0pt 0px; FONT: bold 10pt Times New Roman, Times, Serif"   align="justify"&gt;&lt;i&gt;Recently Issued Accounting  Pronouncements&lt;/i&gt;&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt;TEXT-INDENT: 0in; MARGIN: 0pt 0px; FONT: bold 10pt Times New Roman, Times, Serif"   align="justify"&gt;&amp;#160;&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt;TEXT-INDENT: 0.5in; MARGIN: 0pt 0px; FONT: 10pt Times New Roman, Times, Serif"   align="justify"&gt;In February 2013, the FASB issued ASU 2013-02  "Reporting of Amounts Reclassified Out of Accumulated Other  Comprehensive Income" (ASU 2013-02). ASU 2013-02 amends ASU 2011-05  and requires that entities disclose additional information about  amounts reclassified out of Accumulated Other Comprehensive Income  (AOCI) by component. Significant amounts reclassified out of AOCI  are required to be presented either on the face of the Consolidated  Statements of Income and Comprehensive Income or in the notes to  the financial statements. The requirements of ASU 2013-02 are  effective for fiscal years and interim periods in those years  beginning after December 15, 2012. The Company does not expect the  adoption of ASU 2013-02 to have a material impact on the  Company&amp;#8217;s financial statements.&lt;/div&gt;    &lt;div style="clear:both; FONT-FAMILY:Times New Roman;FONT-SIZE: 10pt"&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 organization, consolidation and basis of presentation of financial statements disclosure.</ElementDefenition><ElementReferences>Reference 1: http://www.xbrl.org/2003/role/presentationRef

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