Despite the evaluation of many different chemotherapy and immunotherapy drugs, the median survival in metastatic melanoma remains in the range of 6 to 9 months. Combination chemotherapy or combination immunotherapy has not produced a significant advantage over single-agent therapy but is associated with greater toxicity. Based on the potential for additive or synergistic activity with the combination of chemotherapy and biotherapy, many investigators have evaluated biochemotherapy in patients with advanced melanoma. Aggregate results suggest that biochemotherapy is tolerable and produces a response rate in the range of 50% with a complete response rate of 10%. Although these phase II results appear superior to previous results with chemotherapy or immunotherapy alone, the true benefits of biochemotherapy can only be determined with the results of randomized phase III trials; therefore, biochemotherapy should be considered an as yet experimental therapy. Many other issues regarding biochemotherapy, such as sequence, outpatient administration, and use in the adjuvant setting, for stage III melanoma are being actively evaluated. Copyright 2002, Elsevier Science (USA). All rights reserved.