The incidence of melanoma is increasing and it is estimated that, in the United States, the lifetime risk of developing melanoma is 1 in 55. There have been many randomized trials that have refined the treatment and minimized the morbidity of the intervention of this prevalent disease. From 1975 to 2000, there were 154 prospective randomized trials on the treatment of local, regional, and metastatic melanoma. Between 2001 and the end of 2008, there were 52 randomized controlled trials relating to the treatment of patients with malignant melanoma. This article reviews the results of the major studies included in the prior article, and provides a detailed description of selected randomized controlled trials performed from 2001 to 2008.