The promise of DNA vaccines is as compelling today as it was more than a decade ago. Ease of manufacture, stability at ambient temperatures without the need for a cold chain and its ability to mimic natural infections and elicit appropriate immune responses makes this vaccine platform extremely attractive. Although, human clinical trials of DNA vaccines have yielded less than optimal results, the approval and licensing of a few veterinary vaccines is testimony to the proof-of-concept and the hope that licensed DNA vaccines for human use may not be too far away. Delivery and targeting of immunologically relevant cells appears to be the major hurdle in maximizing the immunogenicity of DNA vaccines. Several different approaches that are currently pursued in achieving this objective are discussed.