Oxidative stress seems to play a key role in the pathogenesis of atherosclerosis. Agents that protect low-density lipoprotein from oxidation have been shown in a range of in vitro and animal models to reduce the development and progression of atherosclerosis. These agents include antioxidant micronutrients such as vitamin E. They have gained wide interest because of the potential for prevention of atherosclerotic vascular disease in humans. In the last decade, many trials with antioxidants have been carried out in patients with cardiovascular disease, but the results are equivocal. The reason for the disappointing findings is unclear, but one possible explanation is the lack of identification criteria of patients who are potential candidates for antioxidant treatment. This review analyses the data reported so far to determine whether they clearly support the premise that patients at risk of cardiovascular disease may be candidates for antioxidant treatment.