DNA vaccination is based on the observation that plasmid DNA could directly transfect muscle cells, dendritic cells, and other cell types in vivo. Intramuscular, intraepidermal, or oral application of expression plasmids can induce humoral and cellular immune responses against the encoded proteins. This strategy has now been used to elicit protective antibody and cellular immune responses in a wide variety of preclinical animal models for viral, bacterial, parasitic, and malignant diseases. DNA vaccination is particularly useful for the induction of cytotoxic T cells and may, therefore, have therapeutic potential as well. This was recently demonstrated in an animal model of tuberculosis. Early phase human trials are in progress. The results from these trials may be eagerly awaited.