Melanoma is a particularly aggressive type of skin cancer, and its incidence has been increasing steadily since the 1970s. This article will review the extensive epidemiologic data demonstrating that ultraviolet radiation (UVR) exposure, from the sun or artificial tanning beds, is the most important environmental risk factor for melanoma; the multiple detrimental effects of UVR on human skin, including DNA damage through the formation of dimeric photoproducts, gene mutations, oxidative stress, inflammation, and immunosuppression, all of which contribute to melanomagenesis; and the evidence that protection from UVR exposure, whether by melanin or by sunscreen, reduces the risk of developing melanoma. Semin Cutan Med Surg 30:222-228 © 2011 Elsevier Inc. All rights reserved.