The widespread introduction of effective combination antiretroviral therapy (cART) has had a major influence on the epidemiology and natural history of AIDS-associated Kaposi's sarcoma (AIDS-KS). cART has reduced the incidence of AIDS-KS, and it has been shown to be an effective treatment for early-stage KS. So with the widespread availability of cART, is systemic chemotherapy still required for AIDS-KS? Two indications appear to remain: advanced-stage AIDS-KS and patients who have progressive KS despite effective cART including immune reconstitution inflammatory syndrome KS.