Significant progress made in the field of tumor immunology by the characterization of a large number of tumor antigens, and the better understanding of the mechanisms preventing immune responses to malignancies has led to the extensive study of cancer immunization approaches such as DNA vaccines encoding tumor antigens. This article reviews major aspects of DNA immunization in cancer. It gives a brief history and then discusses the proposed mechanism of action, preclinical and clinical studies, and methods of enhancing the immune responses induced by DNA vaccines.