HIV infection is accompanied by a vigorous immune response to the virus consisting of humoral and cellular elements that effectively neutralize virus infectivity and lyse infected cells when analyzed in cell culture models. However, this immune response shows no evidence of being able to eliminate the infection. The inability to clear this infection places HIV in a category of viruses for which vaccines have yet to be successfully developed. Indeed, effective vaccines have emerged only for viruses where natural immunity is part of the pathogenic process; it is such immunity that became the guiding principle for the development of the respective vaccines. It follows that the unique features of HIV infection and pathogenesis are issues to consider carefully in formulating vaccine strategies, particularly those that relate to its susceptibility to immune attack on the one hand, and its mechanisms of immune escape on the other.