The discovery that mice lacking rods and cones are capable of regulating their circadian rhythms by light provided the conceptual framework for the discovery of an entirely new photoreceptor system within the mammalian eye. We now know that a small subset of retinal ganglion cells are directly photosensitive and utilize an opsin/vitamin A-based photopigment called melanopsin maximally sensitive in the blue part of the spectrum. We also know that these photosensitive retinal ganglion cells mediate a broad range of physiological responses to light, ranging from the regulation of circadian rhythms to pupil constriction. Most recently, it has become clear that the melanopsins are only distantly related to visual pigments and in terms of their biochemistry share more in common with invertebrate photopigments. Here we outline the discovery of this remarkable new photoreceptor system, review the structure of melanopsin and conclude with a working model of melanopsin phototransduction.