Vertebrate vision begins with the absorption of light by visual pigments in photoreceptor cells. Visual pigments, or opsins, are seven membrane spanning, G protein-coupled receptors located in the membrane of the outer segment discs of rods and cones. In the dark, the light sensitive chromophore 11-cis-retinal is covalently attached to opsin through a Schiff base linkage to a specific lysine residue located in the center of the seventh transmembrane alpha helix. Light stimulation results in isomerization of 11-cis-retinal to all-trans-retinal, which causes a change in the conformation of rhodopsin. The resulting photoactivated metarhodopsin II interacts with the G protein transducin and triggers the phototransduction cascade leading to hyperpolarization of photoreceptors and ultimately to inhibition of neurotransmitter release at the synaptic terminus. After isomerization of 11-cis-retinal to the trans configuration, the Schiff base is hydrolyzed and the photolyzed chromophore separates from opsin. Whether all-trans-retinal is released in the lumen of the discs and subsequently transported to the cytosol by the retinal ATP-binding cassette transporter (ABCR)1 or directly released into the cytosol2 is controversial. Cytosolic all-trans-retinal is then reduced to all-trans-retinol by a retinol dehydrogenase (RDH) located in the membrane of the photoreceptor outer segment discs. This or these enzymes have not yet been identified. However, six distinct RDHs expressed in photoreceptors have recently been cloned (Table 70.1). Their functions, in vivo, are unknown, but all of them were shown to reduce all-trans-retinal in vitro.