According to the National Cancer Institute PDQ database, advanced melanoma is refractory to most standard systemic therapy, and all newly diagnosed patients should be considered candidates for clinical trials. Although advanced melanoma is relatively resistant to therapy, several biologic response modifiers and cytotoxic agents have been reported to produce objective responses. Once melanoma is metastatic, treatments are palliative rather than curative. In spite of many attempts at multimodality therapy, the prognosis in this disease remains poor. Further agents are needed if progress is to be made with melanoma treatment.