Ischemic disorders of the retina and optic nerve head (OPH) constitute a common cause of visual loss in the middle-aged and elderly population. These disorders have a high association with atherosclerosis. This review has considered the various aspects of atherosclerosis and its role, as well as that of serotonin, in the development of ischemic disorders of the retina and ONH. It is known that when platelets aggregate on an atheromatous plaque, serotonin is one of the agents released. Studies in experimental atherosclerotic monkeys have shown that, although serotonin has no effect on ocular vasculature in normal monkeys, in atherosclerotic monkeys it produces vasopasm of the central retinal artery (CRA) and/or posterior ciliary artery (PCA) in various combinations but not vasopasm of the arterioles in the retina; vasospasm of the CRA and/or PCA(s) can consequently cause transient, complete occlusion or impaired blood flow in these arteries. It is postulated that in some atherosclerotic individuals this mechanism may play an important role in the development of ischemic disorders of the retina and ONH, including amaurosis fugax, (CRA) occlusion and anterior ischemic optic neuropathy, and possibly also glaucomatous optic neuropathy, particularly in normal tension glaucoma. Studies have also shown that dietary treatment of atherosclerosis abolishes or markedly improves the serotonin induced vasoconstriction within a few months. All these considerations may have important implications for our understanding of the pathogenesis and management of these blinding disorders.