One in three Americans will eventually die of cardiovascular disease. Antioxidant vitamins, which are postulated to reduce risk by about 20-30%, could have substantial clinical and public health impact. Basic research, clinical observation, and epidemiology have contributed to an emerging body of evidence on the atherogenicity of oxidized low-density lipoprotein, which could be an important mechanism to explain why antioxidant vitamins may decrease risk of coronary disease. The antioxidant-vitamin/cardiovascular-disease hypothesis has recently been explored in several large prospective cohort studies, but the findings were not all consistent. In several randomized, small-scale trials using subjects with existing vascular disease, data indicate benefits associated with vitamin E and beta carotene. Over the next several years, data from a number of ongoing primary prevention trials and proposed secondary prevention trials should determine whether antioxidant vitamins decrease risk of vascular disease.