The field of DNA vaccines continues to advance and several new strategies to augment the immunogenicity of DNA vaccines are under evaluation. The majority of these studies are in the early preclinical stage, but some DNA vaccines have moved into clinical trials. In this review, we describe some of the more recent efforts aimed at increasing the immunogenicity of DNA vaccines, including the use of genetic adjuvants and plasmid-based expression of viral replicons. In addition, we discuss the possibility of using DNA vaccines to address emerging infectious agents where they may provide an advantage over other vaccine strategies and we review some areas where DNA vaccines have been used to target self-antigens.