Considerable progress has been made over the past several years in the development of an HIV vaccine. As a result, a growing number of vaccine modalities are being investigated in pre-clinical and phase I/II clinical trials. However, a number of major scientific challenges still remain. It is widely believed that the ideal vaccine should elicit both neutralizing antibodies and cytotoxic T lymphocytes (CTL) against diverse isolates of HIV, but the precise correlates of immunity have not been defined. Recombinant live vector-based vaccines and plasmid DNA vaccines have been shown to induce CTL, either alone or in combination, and these CTL-based vaccines have shown partial protective efficacy in nonhuman primates challenge studies. An immunogen that elicits broadly reactive neutralizing antibodies, however, has yet to be developed.