The development of a safe and effective vaccine for the prevention of AIDS has thus far proven to be extremely difficult, at least in part due to complexities associated with HIV-1 and its pathogenesis. The recent description of individuals transiently infected with HIV-1, as well as persons who survived HIV-1 infection for more than 15 years, indicates the ability of the immune response of certain individuals to control HIV-1 infection. Moreover, vaccination-challenge experiments in macaques infected with simian immunodeficiency virus have shown that protection against infection or development of disease may be achieved in the absence of sterilizing immunity, suggesting that the goals for AIDS vaccine development may have to be redefined. In addition, evaluation of new lentivirus vaccine strategies may largely benefit from the use of the newly developed chimeric simian-human immunodeficiency viruses, allowing the testing of HIV-1 antigen based vaccines in macaques.