The plaque that is the cause of atherosclerosis consists of cholesterol, calcium, fat, and other substances, and it can harder over time. The changes in a person’s arteries disrupt the flow of blood around the body and increase the risk of complications, such as heart attack or stroke. These complications can be life threatening. Cardiovascular disease is the leading cause of morbidity and mortality in the Western world. There is compelling evidence incriminating oxidative stress in the pathogenesis of the atherosclerotic lesion. Several lines of evidence suggest that antioxidants, especially α-tocopherol, have potential beneficial effects with regard to cardiovascular disease. In vitro, α-tocopherol has been shown to inhibit platelet adhesion and aggregation and smooth muscle cell proliferation, exert anti-inflammatory effects on monocytes, and improve endothelial function. Also, supplementation with α-tocopherol has been shown to decrease lipid peroxidation, platelet aggregation, and pro-inflammatory activity of monocytes. However, clinical trials with α-tocopherol supplementation to date have been equivocal. Thus, although mounting in vitro evidence and animal models provide a sound scientific basis for α-tocopherol supplementation, further clinical trials are required before a definitive recommendation can be made with respect to the primary and secondary prevention of heart disease.