The onset of the AIDS epidemic in 1981 was followed by descriptions of many opportunistic infections as well as several unusual cancers. Non-Hodgkin's lymphoma (NHL) was classified as an AIDS-defining illness within 4 years, and is up to 200 times more common in HIV-positive patients. Immunotherapy for cancer has a surprisingly long heritage, but it is only recently that this approach has become established in oncology practice. Here, against a background of the history of immunotherapy, we review clinicopathological features of HIV-associated NHL and discuss current cancer immunotherapeutic treatments including immune reconstitution using highly active antiretroviral therapy (HAART), anti-CD20 monoclonal antibodies, radioimmunotherapy, stem cell transplantation, cytokine therapy and vaccination. As the prognosis for HIV-associated NHL nears that of the general population, these approaches are of increasing importance and value.