Historically, animal model systems have been important components of biomedical research, and the same is proving true for research directed at the human immunodeficiency virus (HIV) pandemic. The most relevant and valuable models for studying infection by HIV-1 and HIV-2 and progression to AIDS involve infection of nonhuman primates with HIV-1, HIV-2, or some of the closely related simian immunodeficiency viruses (SIVs). The SIV macaque model has proven valuable in all aspects of AIDS-related research, with primary emphasis on defining pathogenic properties of lentiretroviruses and on testing novel approaches for prophylactic and therapeutic intervention. Because of certain limitations with the HIV-1 chimpanzee model, not the least of which is the expense involved, the use of HIV-naive chimpanzees should be limited to experiments related to vaccine development, an area for which their value has been demonstrated. Continued efforts to halt the spread of HIV infection and progression of HIV-related diseases will require further use of these animal models.