Advanced melanoma is one of the most chemo-resistant types of human cancers. The incidence increases by about 2.5% on an annual basis, with may partially be related to aging and growth of the population, as well as other environmental risk factors. Virtually no recent progress has been made in the treatment of patients with this disease. In the past 30 years, the FDA has approved only 2 agents, dacarbazine and interleukin-2, on the basis of overall response and response duration, respectively. However, these outcomes were not accompanied by a survival benefit. The most recent randomized study of Dacarbazine (DTIC) yielded an overall response rate of 7%, and to date, no other treatments, including combination therapies, have shown to improve survival when compared to DTIC alone. Hence, the mainstay of treatment for patients with advanced melanoma is DTIC-based therapy.