The incidence and mortality rates of melanoma have increased at annual rates of 2%-3% for the last 30 years. Disseminated disease is largely refractory to cytotoxic chemotherapy and is almost universally fatal. Several recent advances in melanoma biology offer new strategies for potentially treating this aggressive malignancy. This review focuses on three significant advances involving tumor initiation, etiology, and progression. New experimental models reveal a direct role for UV-B light in initiating melanomas in human skin. Studies on E-and N-cadherin elucidate the importance of local homeostatic mechanisms in regulating tumor progression. Finally, several discoveries concerning apoptotic mechanisms in melanoma suggest strategies for future treatments.