The treatment of patients with metastatic melanoma remains a difficult problem. It is clear that more effective agents need to be developed. No single agent in conventional doses has been shown to be more effective than DTIC alone. The results obtained with detrorubicin in untreated patients are encouraging, but need further confirmation. If confirmed, combination regimens incorporating detrorubicin should be studied. Further experience is needed with high-dose cisplatin before it can be recommended for broader clinical use. Recent experience with the 4 drug combination of DTIC, BCNU, cisplatin, and tamoxifen is encouraging. The objective response rate is approximately 50% and patients with visceral disease have demonstrated regressions. CRs are not uncommon with occasional patients exhibiting durable remissions for as long as 3 years. An added benefit is that this regimen is well tolerated by most patients making it technically easy to administer. Finally, the role of interferon needs further study. The response rate to interferon alfa-2a is reasonably well defined at about 20%. Combinations of chemotherapeutic agents and interferons have only begun to be evaluated but the preliminary data are interesting.