Kaposi's sarcoma (KS) is the most common tumor seen in patients with HIV-1 infection. KS causes significant morbidity and mortality through involvement of the skin and visceral organs. The optimal treatment for KS depends on the extent of the disease and immunologic status. However, with knowledge gained on the pathogenesis of disease, newer therapies and compounds are being developed. Early disease patients are best treated with either local therapy or agents that have low toxicity and can be delivered long term. Advanced disease, such as in patients with widespread mucocutaneous disease, lymphedema, and visceral disease, are treated most effectively with cytotoxic agents such as liposomal anthracyclines, vinca alkaloids, or paclitaxel. Future treatment developments are focusing on the role of effective anti-HIV therapy and anti-human herpesvirus (HHV)-8 therapy in an effort to interfere with key steps in the etiology of KS to control the disease. Secondly, agents that focus on the interruption of autocrine and paracrine growth factors such as vascular endothelial cell growth factor and basic fibroblast growth factor, interleukin-6, and interleukin-8 are of therapeutic interest. Some of these compounds currently under evaluation include antiangiogenesis inhibitors and retinoids.