Two recently completed phase I clinical trials with candidate HIV-1 vaccines demonstrated that DNA vaccines are, indeed, immunogenic in humans, even when administered through routine needle injections. However, the best use of this evolving technology lies in its potential to prime the host's immune system. Since the discovery of DNA immunization as a new method of vaccination in the early 1990s, the real value of this technology for human vaccine development was questioned due to the apparent poor immunogenicity in repeated early phase clinical studies when DNA plasmids were injected into humans by conventional needle injections. New results indicate that DNA vaccination can provide excellent priming effects to the human immune system, and high level, antigen-specific antibody and T cell immune responses are elicited upon further stimulation through the employment of a different form of vaccine which contains antigens that match those included in the original priming DNA vaccine formulation. These findings in no way will reduce the value of DNA vaccines, instead, the roles of DNA vaccines should be redefined. It is very likely that DNA vaccine can be most useful by providing an antigen-specific immunologic help to other types of vaccines that are known to have low immunogenicity, including inactivated or recombinant protein-based subunit vaccines.