At least six light-regulated phenomena are preserved in the eyes of retinally degenerate mice, including the entrainment of circadian rhythms, the gating of ocular immune response, and pupillary reactivity. Some of these phenomena have also been observed in blind human patients. These findings have prompted the search for a non-visual ocular phototransduction mechanism. Molecular genetic studies have identified several candidate genes for these effects. These include genes encoding novel ocular opsins, such as melanopsin, as well as potential flavin-based photopigments. Data linking these potential photoreceptors to these phenomena are discussed, and the clinical implications of these findings are explored.