Until the late 1990’s it seemed inconceivable to most vision biologists that there could be an unrecognised class of photoreceptor within the vertebrate eye. After all, the eye was the best understood part of the central nervous system. One hundred and fifty years of research had explained how we see: Photons are detected by the rods and cones and their graded potentials are assembled into an “image” by inner retinal neurones, followed by advanced visual processing in the brain. The eye and the brain are connected via the retinal ganglion cells (RGCs) whose topographically mapped axons form the optic nerve. This representation of the eye left no room for an additional class of ocular photoreceptor. However, attempts to understand how endogenous 24h body clocks (circadian clocks) are regulated by light overturned this conventional view of retinal organisation. We now know that the rods and cones are not the only photosensory neurones of the vertebrate eye. The discovery that mice entirely lacking rods and cones are capable of regulating their circadian rhythms by light provided the conceptual framework for the discovery for an entirely new photoreceptor system within the mammalian eye. A small sub-set of retinal ganglion cells are directly photosensitive and utilize an opsin/vitamin A based photopigment called melanopsin (Opn4) maximally sensitive in the blue part of the spectrum. These photosensitive retinal ganglion cells (pRGCs) 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 common with invertebrate photopigments rather than their rod- and cone-opsin companions within the retina. This presentation will outline the discovery of this remarkable new photoreceptor system, review how melanopsin might transduce light into a physiological response and consider how our understanding of this new photoreceptor system is beginning to inform clinical practice.