Angiogenesis is a process that is central to tumor growth and survival. This process is stimulated by a variety of intrinsic growth factors such as vascular endothelial growth factor, basic and acid fibroblast growth factor, and platelet-derived endothelial growth factor, among others. The process of neo-angiogenesis has been shown to be key in the proliferation of melanoma, and primarily believed to be so in the metastatic process. Biologic markers of angiogenesis are being evaluated for correlations with prognosis and biologic behavior of the tumor. These markers may also indicate susceptibility to targeted therapy. Interruption of the tumor-sustaining process of angiogenesis has become a major focus of anticancer drug development. Promising agents are in both preclinical and clinical development. Several may prove to be clinically important.