Recent advances in immunobiology have led to a greater understanding of the healthy immune system and the complex pathogenesis of human immunodeficiency virus (HIV) infection. Knowledge of the mechanisms underlying the decrease in CD4+ T cells is rapidly evolving as a result of new assays, genetic advances, and recombinant DNA technologies. Studying the immune responses of long-term non-progressors is also providing insight into the immunopathology of HIV. Trials using highly active antiretroviral therapy and immune modulators have shown that it may be possible to reverse damage to the immune system and increase CD4+ T-cell numbers. Current and future findings might provide the knowledge necessary to identify effective HIV drugs and vaccines with acceptable toxicity profiles and to determine whether it will be possible to fully restore immune system function in patients with HIV disease.