Kaposi's sarcoma (KS) is the most common malignancy associated with human immunodeficiency virus-1 (HIV-1) infection and can result in significant morbidity. The clinical course of KS is quite variable, although for the majority of patients, KS is ultimately a progressive disease requiring systemic therapy. For early indolent KS, local therapies may be appropriate and may provide significant palliation. For patients with more advanced or rapidly progressive disease, systemic therapy is the treatment of choice. Interferon-alfa (Intron A, Roferon-A), with or without antiretroviral agents, is particularly useful for patients with relatively preserved immune function. For patients with symptomatic visceral disease, pulmonary disease, or rapidly progressive cutaneous disease, chemotherapy is the treatment of choice. An increasing number of agents are now available for the treatment of KS. Pathogenesis-based treatment and/or preventive therapies based on the recognized association between KS-associated herpesvirus (KSHV) and KS are likely to be available in the near future.