The combination of cisplatin-based chemotherapy with interleukin-2 and interferon-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. Although the results of the phase II single institutional studies were encouraging, phase III studies have not shown consistent results. Many factors may explain this finding including small number of patients, lack of a proper phase II study to define the antitumor activity of a given biochemotherapy regimen, and principally lack of a multicenter phase II study to better define the response rate as well as to gain experience with an IL-2-based regimen in the community setting prior to conducting a phase III trial. Large randomized studies are ongoing and should better clarify the long-term impact of biochemotherapy on survival in patients with advanced melanoma.