A new mammalian photoreceptor was recently discovered to reside in the ganglion cell layer of the inner retina. These intrinsically photosensitive retinal ganglion cells (ipRGCs) express a photopigment, melanopsin that confers upon them the ability to respond to light in the absence of all rod and cone photoreceptor input. Although relatively few in number, ipRGCs extend their dendrites across large expanses of the retina making them ideally suited to function as irradiance detectors to assess changes in ambient light levels. Phototransduction in ipRGCs appears to be mediated by transient receptor potential channels more closely resembling the phototransduction cascade of invertebrate than vertebrate photoreceptors. ipRGCs convey irradiance information centrally via the optic nerve to influence several functions. ipRGCs are the primary retinal input to the hypothalamic suprachiasmatic nucleus (SCN), a circadian oscillator and biological clock, and this input entrains the SCN to the day/night cycle. ipRGCs contribute irradiance signals that regulate pupil size and they also provide signals that interface with the autonomic nervous system to regulate rhythmic gene activity in major organs of the body. ipRGCs also provide excitatory drive to dopaminergic amacrine cells in the retina, providing a novel basis for the restructuring of retinal circuits by light. Here we review the ground-breaking discoveries, current progress and directions for future investigation.