Although it is not clear what arm of the immune response correlates with protection from HIV-1 infection or disease, a robust broad cellular and humoral immune response will likely be needed to control this infection. Accordingly, it is crucial to characterize which HIV-1 gene products are potential targets to elicit these responses. DNA vaccination has been shown to be effective for induction of both humoral and cellular immune responses in animal models. Most DNA vaccine strategies studied to date have been based on targeting structural HIV-1 proteins, but others have focused on the regulatory/accessory HIV-1 proteins as an approach to induce immune responses able to recognize early infected cells. It has also become clear that HIV-DNA vaccine efficacy in humans requires improvement. Combinations of HIV-1 genes, improvement of the DNA vector itself, or addition of genetic adjuvants (cytokines or costimulatory molecules) as part of the DNA vaccine itself, have been evaluated by several groups as approaches for enhancing DNA vaccine-induced immune responses. Encouraging results have been obtained in primate models, supporting that these strategies should be further evaluated in humans, for either prophylaxis or immune therapy of HIV-1.