Kaposi's sarcoma (KS) is a disease characterized by proliferative vascular lesions, which almost invariably contain the KS-associated herpesvirus (KSHV), also called human herpesvirus 8. KSHV is a lymphotrophic and angiotrophic herpesvirus, whose genome encodes several proteins involved in proliferation, antiapoptotic functions, and inflammation. Most KS spindle cells express latent KSHV genes, but a few express lytic genes, which might be involved in angiogenic and paracrine mechanisms that contribute to KS pathogenesis. A number of tissue culture and mouse models have been established, but a comprehensive system that accurately portrays KS pathogenesis still does not exist.