Melatonin is an endogenous hormone commonly associated with regulation of sleep. However, over the last two decades, research has elucidated a range of effects associated with the compound, including anti-inflammatory, both direct and indirect antioxidant activity, tissue regenerative benefits, and preservation of mitochondrial function. Melatonin's anti-inflammatory and antioxidant support, coupled with its mitochondrial support, make it an intriguing target for use to support skin health. Human skin and hair follicles express functional melatonin receptors. They also engage in substantial melatonin synthesis. By supporting cutaneous homeostasis, melatonin and its metabolites are thought to attenuate carcinogenesis and possibly other pathological processes, including hyperproliferative/inflammatory conditions. The primary extrinsic driver of aging has been considered to be exposure to ultraviolet (UV) light, which is well-established to contribute to sunburn, immunosuppression, skin aging, and carcinogenesis. Topically applied melatonin has been shown to reduce markers of reactive oxygen species formation and to reverse signs of skin aging. As the global population continues to age, photo-damage remains a significant cutaneous concern. While use of sunscreens and UV avoidance strategies are essential to mitigate skin cancer risks, the potential to protect the skin and improve the appearance of photo-damage through the use of topical antioxidant support is appealing. The evidence suggests that melatonin deserves consideration for topical use as an anti-aging and skin protective agent. It is shown to be both safe and effective when topically applied. J Drugs Dermatol. 2018;17(8):966-969.