HIV infection is associated with an extremely vigorous virus-specific cytotoxic T-lymphocyte (CTL) response. This CTL activity is of sufficient magnitude to be detected using freshly isolated peripheral blood mononuclear cells, but despite this vigorous immune response, HIV-1 disease ultimately progresses. This article describes methods used to detect CTL responses and epitopes recognized by HIV-1 specific CTL. The potential role of CTL in the control of viral replication, disease pathogenesis, and possible mechanisms that allow HIV-1 to ultimately evade the host's immune response is discussed. Finally, efforts to induce CTL responses through vaccines are summarized.