The recent developments of viral based vectors in design, in biosafety and in accomplishing high transfection efficiency for transgene expression into target cells makes them attractive tool for various gene transfer applications. Several kinds of viruses, including HIV derived Lentivirus vectors (LVs), non-HIV based Retroviruses, Adenoviruses, Adeno-associated viruses, Baculovirus and Herpes simplex viruses have been manipulated for use in gene transfer and gene therapy purposes. Each viral vector system is integrated with a distinctive in built properties that affect its suitability for specific gene therapy purposes. Although LVs offered many unique solutions for advanced gene therapy research and clinical applications, however, several important issues of LVs gene therapy must be overcome before it gains widespread use. Nonetheless, the number of promising gene therapy studies in progress are highly encouraging and outcome from these clinical trials will provide valuable insights particularly for the clinical suitability and safety profile of LVs. This review contain a comprehensive discussion starting with the general background of the field thereafter discussing the salient features of recent developments in viral vector system in general and with special focus on LVs.