Recently published literature has provided evidence that the unfolded protein response (UPR) is involved in the development of retinal degeneration. The scope of these studies encompassed diabetic retinopathy, retinopathy of prematurity, glaucoma, retinal detachment, light-induced retinal degeneration, age-related macular degeneration, and inherited retinal degeneration. Subsequent studies investigating the role of individual UPR markers in retinal pathogenesis and examining the therapeutic potential of reprogramming the UPR as a method for modulating the rate of retinal degeneration have been initiated. Manipulation of UPR markers has been made possible by the use of knockout mice, pharmacological agents, and viral vector-mediated augmentation of gene expression. Future research will aim at identifying specific inhibitors and/or inducers of UPR regulatory markers as well as expand the list of UPR-related animal models. Additionally, adeno-associated virus-mediated gene delivery is a safe and effective method for modulating gene expression, and thus is a useful research tool for manipulating individual UPR markers in affected retinas and a promising delivery vector for gene therapy in retinal degenerative disorders. © 2013 Molecular Vision.