The combination of cisplatin-based chemotherapy with interleukin 2 (IL-2) and IFN-alpha, referred to as biochemotherapy or chemoimmunotherapy, has shown promising antitumor activity in patients with metastatic melanoma. Phase II studies have reported overall response rates ranging from 40 to 60%, with durable complete remissions in approximately 10% of the patients. Toxicity, however, is often severe and can be life-threatening if the healthcare team is not familiar with toxicity management. In this report, we briefly describe the clinical results of the most effective biochemotherapy regimens and provide a detailed description and management of the most common toxic effects, with emphasis on the concurrent biochemotherapy program initially developed at M. D. Anderson Cancer Center and currently being tested in a slightly modified version in two large-scale Intergroup Phase III trials.