Combination therapy with protease inhibitors and nucleoside analogues dramatically suppresses plasma HIV-1 RNA and delays progression to AIDS, but the impact on HIV-associated malignancy remains to be established. Observational and time-trend data indicate that the incidence of Kaposi's sarcoma (KS) and primary brain lymphoma have decreased, but suggest that current therapies have not had a proportionate effect on systemic non-Hodgkin's lymphomas (NHL). As opportunistic infection and mortality are yielding to advances in antiretroviral therapy, lymphoma may increase in importance as a cause of AIDS-related morbidity and mortality. Further improvements in the long-term consequences of HIV infection will depend on better prevention and treatment of this serious malignant complication.