DNA vaccines, also referred to as genetic, plasmid or polynucleotide vaccines, represent a relatively simple and economical method to exploit gene transfer for immunization against tumor associated antigens. This review discusses the potential advantages of DNA vaccines for cancer immunotherapy as compared to conventional protein vaccines and viral vectors. The proposed mechanisms responsible for induction of immune responses following DNA-based immunization are summarized. The preclinical development of DNA vaccines and the clinical experience with DNA immunization for cancer to date are reviewed. The low toxicity associated with DNA vaccines favors its further development, but additional strategies to improve the potency of this approach are needed if it is to be successfully integrated into the clinical setting.