A small subset of retinal ganglion cells projecting to the suprachiasmatic nucleus and other brain areas, is implicated in non-image forming visual responses to environmental light such as the pupillary light reflex, seasonal adaptations in physiology, photic inhibition of nocturnal melatonin release, and modulation of sleep, alertness and activity. These cells are intrinsically photosensitive (ipRGCs) and express an opsin-like photopigment called melanopsin. Two recent studies utilizing selective genetic ablation of ipRGCs demonstrate the key role of these inner retinal cells in conveying luminance signals to the brain for non-image forming visual processing. These findings advance our understanding of functional organization of a novel photosensory system in the mammalian retina, demonstrating well-defined roles for ipRGCs in circadian timing and other homeostatic functions related to ambient illumination.