Sponsor of Abbreviated New Drug Application (ANDA) is responsible for submitting the sufficient information which demonstrates that their proposed generic version is equivalent to Reference Listed Drug (RLD) in quality, safety & efficacy with enhanced awareness in pharmaceutical industry and regulatory agencies after Ritonavir history in 1998, Polymorphism evolved out as a major point of attention for industry as well as regulatory agencies. Many pharmaceutical compounds exist in different crystalline forms and thus exhibit polymorphism. Polymorphism may affect Chemical and Physical Stability, Apparent Solubility, Dissolution, Bioavailability and Bioequivalence and Manufacturability of drug product, which require special attention during product development as it affects the quality, safety and efficacy of drug product. In addition to this, impact of polymorphism, monitoring and control of polymorphism and reporting scheme of polymorphic information in Abbreviated New Drug Application (ANDA) are also covered in this review. Careful attention is given to the issue of irrelevance of polymorphism for establishing drug substance “sameness”. For better understanding, case studies are also provided for scientific and regulatory assessment of polymorphism in Abbreviated New Drug Application (ANDA).