The incidence of melanoma has been rising during the past 40 years and may be the result of lifestyle changes that have led to an increased sun exposure in fair-skinned people. Ultraviolet radiation (UVR) is believed to be the main causative factor in melanoma development with an acute intermittent exposure being more relevant than a chronic cumulative one. While UVB (280-320 nm) can directly cause DNA damage (UVB fingerprint mutations) in the cells of the epidermis, UVA (320-400 nm) induces damage indirectly by the formation of reactive oxygen species. Since UV-associated mutations are rare in melanoma, it is speculated that UVR supports melanoma development by indirect effects, e.g. immunosuppression or stimulation of growth factors in the skin. Taken together, animal models and epidemiological data suggest a UVA-associated pathogenesis of melanoma that puts into question the effectiveness of sunscreens in melanoma prevention.