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Retinopathy of prematurity (ROP) is a vasoproliferative disease occurring in premature infants that affects the blood vessels of the developing retina. ROP results in the development of vascular shunts, neovascularization, and in its most severe form tractional retinal detachment. The development of retinal vascular shunts and neovascularization in ROP is related to local ischemia in the immature and incompletely vascularized retina. Understanding the pathophysiology of ROP helps physicians both in the prevention and treatment of ROP and will be discussed in this review article. The role of oxygen in the pathophysiology of ROP will be reviewed with recent studies discussed.