Kaposi's sarcoma (KS) remains the most commonly diagnosed malignancy in HIV-infected patients, and is one of the AIDS-defining diagnoses. Several different therapeutic options are available, but the optimal therapy is still unclear. The incidence of KS has sharply declined since highly active antiretroviral therapy (HAART) became widely available, making HAART indispensable in the treatment of epidemic KS. HAART can be given alone or in combination with systemic and local therapy. Systemic therapy can be given in disseminated, progressive or symptomatic disease. Treatment options are interferon-alpha and chemotherapy including pegylated-liposomal anthracyclines and paclitaxel. For local disease, radiotherapy, intralesional chemotherapy or cryotherapy may be used. In resource-limited settings, intravenous vincristine, oral etoposide or intramuscular bleomycin may be feasible options. Other therapies, such as angiogenesis inhibitors, are under investigation in clinical trials.