The understanding that tumor cells can be recognized and eliminated by the immune system has led to intense interest in the development of cancer vaccines. Viruses are naturally occurring agents that cause human disease but have the potential to prevent disease when attenuated forms or subunits are used as vaccines before exposure. A large number of viruses have been engineered as attenuated vaccines for the expression of tumor antigens, immunomodulatory molecules, and as vehicles for direct destruction of tumor cells or expression of highly specific gene products. This article focuses on the major viruses that are under development as cancer vaccines, including the poxviruses, adenoviruses, adeno-associated viruses, herpesviruses, retroviruses, and lentiviruses. The biology supporting these viruses as vaccines is reviewed and clinical progress is reported.