Current therapeutic options for the treatment of advanced melanoma are inadequate. Chemotherapy with dacarbazine remains a 'gold standard' despite no evidence of improved survival or durable remissions. Interleukin (IL)-2 is an immunotherapeutic agent that, when administered in a high-dose bolus schedule, produces a small number of durable remissions in patients with metastatic melanoma, and on this basis it was approved for use in the US in 1998. In randomized clinical trials, IL-2, administered as a continuous infusion either alone or in combination with chemotherapy (biochemotherapy), has not improved response rates over chemotherapy alone. Low-dose IL-2, while less toxic and more convenient, produces low response rates and appears to be ineffective in metastatic melanoma. Newer, innovative approaches such as IL-2 gene therapy and strategies to ameliorate the toxicity of this agent are now being explored in clinical trials.