During the past three decades, non-human primate (NHP) models have gained an increasing importance in HIV basic and translational research. In contrast to natural host models, infection of macaques with virulent simian or simian-human immunodeficiency viruses (SIV, SHIV) results in a disease that closely resembles HIV infection and AIDS. Although there is no perfect animal model, and each of the available models has its benefits and limitations, carefully designed NHP studies with selection of experimental variables have unraveled important questions of basic pathogenesis and have provided the tools to explore and screen intervention strategies. For example, NHP studies have advanced our understanding of the crucial events during early infection, and have provided proof-of-concept of antiretroviral drug treatment and prevention strategies such as pre-exposure prophylaxis (PrEP) regimes that are increasingly used worldwide, and upon overcoming further barriers of implementation, have the potential to make the next generation AIDS-free. Remaining goals include the pursuit of an effective HIV vaccine, and HIV cure strategies that would allow HIV-infected people to ultimately stop taking antiretroviral drugs. Through a reiterative process with feed-back from results of human studies, NHP models can be further validated and strengthened to advance our scientific knowledge and guide clinical trials.