Twenty-five years after the discovery of HIV as the cause of AIDS, tremendous progress has been made in reducing the morbidity and mortality associated with this disease. However, there is still neither a cure nor a vaccine for HIV infection. This shortcoming is likely a consequence of our incomplete understanding of the mechanisms of AIDS pathogenesis, particularly with regard to the interaction between the virus and the host immune system. In this article we review a series of recent advances in specific areas of HIV immunopathogenesis research: virus-host cell interactions; immune responses to HIV; chronic immune activation; and natural simian immunodeficiency virus infections. Finally, we discuss the potential implications of these findings for HIV/AIDS therapy and vaccines.