While sunlight is important for life, ultraviolet radiation (UVR) can have harmful and mutagenic effects. This duality is particularly relevant to human skin, in which UVR both participates in evolutionarily important photochemical reactions yet may act as a potential carcinogen. UVR can upregulate production of melanin, the “tanning response” that serves a photoprotective function. This genetic program is centrally tuned by the transcription factor MITF, a master regulator of melanogenesis and melanocyte function. In this review, we discuss the myriad consequences of UV exposure for skin homeostasis, highlighting the diverse pathways activated by this ultraviolet radiation.