Melanoma and nonmelanoma skin cancers are among the most prevalent cancers in the human population. Solar ultraviolet radiation is considered a major etiological factor but the relationship between dose, timing, and nature of exposure to tumor development is still unclear. Free radicals are generated by normal physiologic processes, including aerobic metabolism and inflammatory response, but may inflict cellular damage when generation is increased and antioxidant defense mechanisms are overwhelmed. Important findings supporting the free radical hypothesis in skin carcinogenesis are: (1) Reactive oxygen species (ROS) are generated in UVA- and UVB-irradiated skin in excessive doses, (2) the natural cutaneous antioxidant defense is impaired upon UV-exposure, (3) free radicals are involved in all steps of carcinogenesis, (4) supplementation with antioxidants can inhibit skin carcinogenesis, and (5) conditions that increase ROS generation enhance photocarcinogenesis. These findings provide a promising rationale for the development of powerful new antioxidant strategies in the prevention and therapy of skin cancer.