The introduction of highly active antiretroviral therapy (HAART) has had a dramatic impact on the morbidity and mortality of individuals living with human immunodeficiency virus (HIV). In addition to contributing to declines in the incidence of several opportunistic infections, HAART is affecting the incidences of several acquired immunodeficiency syndrome (AIDS)-defining malignancies. The incidence of Kaposi's sarcoma (KS) and primary central nervous system lymphoma (PCNSL) has dropped precipitously since the introduction of HAART in 1995. Systemic non-Hodgkin's lymphoma (NHL) appears to be declining in incidence as well, but to a lesser degree than KS and PCNSL. On the contrary, the incidence of invasive cervical carcinoma has not significantly changed in the HAART era. The impact of HAART on the epidemiology of other HIV-associated malignancies, including Hodgkin's disease and anal carcinoma, remains unclear. Data regarding the impact of HAART on the natural history and treatment outcomes of HIV-associated malignancies are limited. The possibility of direct and indirect roles of HIV in HIV-related carcinogenesis suggests that antiretroviral therapy may be an important component of the treatment strategy for several HIV-related malignancies. Patients with HIV-NHL treated with HAART in addition to chemotherapy experience fewer intercurrent opportunistic infections. Furthermore, the simultaneous administration of HAART and chemotherapy does not appear to significantly increase toxicity. Whether the combination of HAART and standard therapy results in improved survival remains uncertain. This two-part article, which will conclude in the May 2002 issue, analyzes the impact of HAARTon the incidence, clinical course, and outcomes of each of the AIDS-related malignancies.