Oxidative stress appears to play a key role in the pathogenesis of atherosclerosis. Agents that prevent the oxidation of low-density lipoprotein have reduced the development and progression of this disease in a range of in vitro experiments and animal models. In the last decade, many trials of antioxidants in patients with cardiovascular disease have been conducted, but the results have been ambiguous. The reason for the disappointing findings is unclear, but one possible explanation is the lack of identification criteria for patients who are potential candidates for antioxidant treatment. This review analyzes data reported to date, in order to determine whether these clearly support the premise that patients at risk of cardiovascular disease may be candidates for this therapeutic option.