The incidence of non-melanoma skin cancer is rising and primary prevention, including the use of sunscreens, has been proven inadequate. Skin cancer strongly correlates with chronic sun exposure. Here we first describe the effects of ultraviolet light on skin: ultraviolet B light can initiate skin tumor development through direct DNA damage and mutation in tumor suppressor and prooncogenes whereas ultraviolet A light is particulary important in causing oxidative stress by inducing reactive oxygen and nitrogen species such as superoxide anion, hydroxyl radical, hydrogen peroxide and nitric oxide. Ultraviolet radiation also causes inflammation and immunosuppression in the skin. The possibilities for photoprotection of the skin are reviewed. A preventive strategy to support the endogenous antioxidant system by topical delivery of various enzymes or non-enzymatic antioxidants is described. The most important enzymatic antioxidants are glutathione peroxidase, catalase, superoxide dismutase and haem-oxygenase. The representatives of non-enzymatic skin antioxidants are glutathione, α-tocopherol, ascorbate, β-carotene, ubiquinon and melanins. Numerous substances, particulary polyphenols, flavonoids and acyclic carotenids, derived from nutrient plants demonstrate strong antioxidant activity, too. Some substances of the natural origin such as curcumin, capsaicin and gingerol have also been shown to reduce photocarcinogenesis, not only because of their antioxidant activity but also due to their capacity to prevent inflammation, gene mutation or immunosuppression. Although the results of preclinical studies are very promising, clinical evidence that natural antioxidants prevent skin cancer is not always convincing.