Atherosclerosis is the leading cause of morbidity and mortality in the United States. Evidence suggests that antioxidants, especially alpha-tocopherol (AT), have potential benefits with respect to cardiovascular disease. AT has been shown to decrease lipid peroxidation, to inhibit platelet adhesion, aggregation, and smooth muscle cell proliferation, to exert anti-inflammatory effects on monocytes, and to improve endothelial function. Low levels of AT are related to a higher incidence of cardiovascular disease and increased intakes appear to afford protection against cardiovascular disease. Although clinical trials with AT supplementation to date have been conflicting, the majority of evidence supports a benefit for AT supplementation in patients with pre-existing cardiovascular disease. Clearly, more clinical trials are required in individuals with increased oxidative stress before a definitive recommendation can be made with respect to AT supplementation in atherosclerosis.