BACKGROUND: Ultraviolet (UV) radiation is the main etiologic factor for skin cancer. The endogenous hormone melatonin has been proposed to have protective effects against sunlight. AIM: The aim of this review was to evaluate melatonin's protective effects against UV radiation and to clarify the cellular mechanisms behind this effect. METHOD: Medline, Embase and Cinahl were searched up to January 2013 to identify studies evaluating melatonin's protective effect against UV radiation (UVR)-induced skin erythema in humans and damage on a cellular level. RESULTS: Four human studies have investigated melatonin's protective effect on UVR-induced skin damage. Melatonin was shown to have protective effects when applied before UVR, but no effect if applied after exposure. A total of 16 experimental studies evaluated melatonin's protective effect against UVR-induced damage to cellular structures and pathways. DISCUSSION/CONCLUSION: The protection against UVR-induced skin damage was conducted by melatonin acting directly as an antioxidant, and indirectly by regulating gene expression and inducing a DNA stabilizing effect. As these results were obtained using artificial UVR and without investigating possible side effects, studies using natural sunlight and evaluating possible side effects of topical melatonin administration are warranted.