In recent years, a number of tumor vaccination strategies have been developed. Most of these rely on the identification of tumor antigens that can be recognized by the immune system. DNA vaccination represents one such approach for the induction of both humoral and cellular immune responses against tumor antigens. Studies in animal models have demonstrated the feasibility of utilizing DNA vaccination to elicit protective antitumor immune responses. However, most tumor antigens expressed by cancer cells in humans are weakly immunogenic, and therefore require the development of strategies to potentiate DNA vaccine efficacy in the clinical setting. This review focuses on recent advances in understanding of the immunology of DNA vaccines, as well as strategies used to increase DNA vaccine potency with respect to cytotoxic T-lymphocyte activity.