The discovery of melanopsin-expressing photosensitive retinal ganglion cells (pRGCs) has led to a fundamental change in our understanding of retinal light detection. pRGCs perform a broad range of non-visual functions — most notably mediating circadian entrainment to the environmental light/dark cycle. However, over the last two decades it has become clear that the melanopsin system is far more complex than first realised, influencing a wide range of physiology and behaviour, including pupillary constriction, light aversion, sleep, learning and memory and even mood. Here we provide an overview of the key areas of physiology known to be mediated by melanopsin pRGCs, as well as emerging translational opportunities.