Systemic therapy for advanced melanoma includes chemotherapy, either with dacarbazine (DTIC) alone or a multiagent combination chemotherapy, and biologic therapy with recombinant interferon-alpha and/or interleukin-2. However, none of these treatment options has produced long-term control of the disease except on rare occasions. Combined chemo-immunotherapy (biochemotherapy) has shown high objective response rates (approximately 50%) and a significant though small proportion of long-term complete responders in metastatic melanoma. It has, however, been associated with greater toxicity. Overall results of sequential versus concurrent biochemotherapy are similar, but the toxicity appears to be less severe in patients treated with the concurrent regimen. At this time, biochemotherapy is under evaluation in a well-designed prospective, randomized trial to identify whether there is benefit to this strategy, compared with chemotherapy alone.