DNA vaccination is a new way to generate antigen specific immune responses by inoculating plasmid DNA encoding microbial genes. We believe that the use of immunologic adjuvants together with DNA vaccines is a promising way to enhance and optimize DNA-derived immunity. Various chemical and genetic adjuvants have been explored in our recent study. Data from these studies suggests that adjuvants exert their immunomodulatory properties through several mechanisms such as lymphoid cells recruitment, cytokine induction, and the facilitation of DNA entry into cells. Furthermore, each adjuvant has unique immunomodulatory effects on cell-mediated and humoral immune responses induced by DNA vaccination to human immunodeficiency virus type 1. To optimize the desirable immune response, the choice of adjuvant and decision of immunization route are important considerations. A similar approach may be useful potentiating anticancer immunotherapy as well.