Kaposi's sarcoma (KS) is still one of the most common malignancies in patients with human immunodeficiency virus (HIV) infection. Large randomized clinical trials have shown a protective effect of combination antiretroviral therapy (cART) against the development of KS, even in patients with a relatively preserved immune system. In patients with sufficient cART, KS has become a rarity. In most patients with HIV-associated KS who initiate cART, the KS lesions stabilize with decreasing HIV plasma viremia and immune reconstitution, or even resolve completely without any specific treatment. In patients with advanced or rapidly progressive disease, especially in the setting of an immune reconstitution syndrome, cART should be combined with cytotoxic chemotherapies. With regard to the KS pathogenesis, several new therapies have been suggested, such as antiviral agents, cytokines, and inhibitors of angiogenesis.