This article provides a review of the current medical management of patients with high-risk and metastatic cutaneous melanoma, including a review of the use of adjuvant interferon therapy and a discussion of adjuvant treatments under evaluation. The use of standard chemotherapeutic agents for metastatic disease is discussed, with an emphasis on developmental therapeutics using targeted agents. This discussion includes a review of the immune therapy for metastatic melanoma, including newer immunomodulatory agents and cellular therapeutics that are expected to significantly impact the care of these patients.