Melanopsin is a fly-like visual pigment (R-type) expressed in a small subset of light-sensitive retinal ganglion cells (ipRGCs) in the mammalian retina. It is involved in regulating non-image forming visual behaviors, such as circadian photoentrainment and the pupillary light reflex (PLR), as well as aspects of image-forming vision. ipRGCs act as autonomous photoreceptors via the intrinsic melanopsin-based phototransduction pathway and as a relay for rod/cone input via synaptically driven responses. The regulation of melanopsin by phosphorylation profoundly effects its kinetics. C-terminal phosphorylation of melanopsin determines the recovery kinetics of the intrinsic melanopsin-based photo response in ipRGCs, the duration of the PLR, and the speed of reentrainment. RGS proteins are also involved in modulating light-activated melanopsin. Understanding the biochemistry of the visual pigment melanopsin leads to insights into the physiology and behavior associated with ipRGCs.