After almost 20 years of research, DNA vaccination is still a relatively young technique in the vaccine-toolbox. DNA vaccines can easily be modified by conventional cloning techniques, are relatively easy to produce and might be particularly useful for therapeutic vaccination against intracellular pathogens and cancer. After the early pre-clinical successes, DNA vaccination moved into the clinic and numerous trials have been performed thus far. In the oncology field, these trials aimed for the induction of cellular immunity directed against tumor specific antigens. Although DNA vaccines proved to be well tolerated, and elicited some immune activation in patients, robust immune activation followed by clinical responses has not been observed yet. Nevertheless, several promising strategies are currently under development to increase the performance of the current generation DNA vaccines. Future research has to demonstrate whether these strategies are able to give DNA vaccination a defined position in cancer treatment.