The advent of highly active antiretroviral therapy (HAART) has lead to a substantial reduction in the prevalence, morbidity, and mortality associated with AIDS-related Kaposi's sarcoma. Similarly, concomitant advances in chemotherapy and supportive-care protocols have allowed for Kaposi's sarcoma to be managed more effectively in comparison with the pre-HAART era. Furthermore, developments in our understanding of the pathogenesis of Kaposi's sarcoma have identified several molecular targets that can potentially provide new therapeutic strategies. This Review discusses the role of conventional chemotherapeutic and immunomodulatory agents in the treatment of Kaposi's sarcoma and summarises the current status and future prospects of novel molecularly targeted agents in the treatment of this disease.