OBJECTIVE We will highlight recent advances in defining the attributes of immune responses that control AIDS virus replication using animal models, and also point out key gaps in our understanding that should be addressed in future research. RESULTS Many different vaccine approaches are currently being evaluated in animal models. Almost all of them elicit strong cellular or humoral immune responses in macaques. Commonly used prime-and-boost strategies have had varying degrees of success in diminishing chronic phase virus loads in vaccinated animals, but few have shown durable reduction in replication of the CCR5-tropic simian immunodeficiency viruses (SIVs) that most closely resemble field isolates of HIV. Investigators are therefore turning to other systems, including live attenuated vaccines and cohorts of spontaneous SIV controllers, to help identify the properties of successful host responses to pathogenic SIV. These responses likely incorporate multiple coordinated effector mechanisms. CONCLUSIONS There is no effective AIDS vaccine on the horizon. CD4+ and CD8+ T cell responses and antibodies have all been implicated in control of SIV replication seen in various experimental systems, but the correlates of protection against AIDS virus replication have not yet been definitively identified. Animal models will remain a necessary component of this research.