Studies of classic, and especially African, Kaposi's sarcoma in the 1970s showed that both forms of the disease respond to cytotoxic chemotherapy. The agents that had proven effective against these forms of neoplasm were among the first to be tried for managing epidemic Kaposi's sarcoma (EKS). Thus far, single-agent regimens using either vinblastine, vincristine, or etoposide have apparently shown the greatest efficacy in AIDS-associated Kaposi's sarcoma, with overall response rates of up to nearly 90% in some trials. Various combination regimens have been studied with a view to reducing side effects, particularly immune suppression, while maintaining overall efficacy. Thus far, only an alternating regimen of vinblastine and vincristine shows promise. Despite intrinsic shortcomings, chemotherapy, using cytotoxics alone or in combination with biologic response modifiers and other modalities, will play a role in managing EKS, even as the search for the optimal regimen continues.