Atherosclerosis, the great killer of Western society, probably is initiated when the balance of subendothelial lipoproteins and oxidation potential is upset. Oxidation products, especially oxidized low‐density lipoprotein, set into motion the cascading of numerous pathways, culminating in the fibrous atherosclerotic plaque. The natural antioxidant system includes enzymes and vitamins A, E, and C. The lipophilic vitamins A and E protect the fatty acid components of lipoproteins and membranes, and vitamin C functions in the aqueous phase both directly and by regenerating oxidized vitamin E. In animal models, the antioxidant vitamins protect lipids and prevent atherosclerosis. Population studies suggest an inverse relationship between atherosclerosis and vitamin levels. Several observational studies and some clinical trials have demonstrated that antioxidant vitamin supplements may prevent atherosclerosis. Although approximately 20% of the United States population regularly consumes vitamin supplements, often in high doses, the antiatherogenic benefits of antioxidant vitamins remain unproved by clinical trials, and the long‐term effects of megadose vitamins are yet undefined.