The hypothesis that antioxidant vitamins might decrease the risk of cardiovascular disease (CVD) is a promising area of research. At present, however, it is far from certain whether antioxidant vitamins confer protection against CVD. Evidence for the antioxidant vitamin-cardiovascular disease hypothesis has accumulated from several lines of research. Laboratory research has identified biochemical properties of antioxidant vitamins that could explain their possible role in inhibiting and delaying coronary atherosclerosis. Epidemiologic studies have provided support for the hypothesis by showing that people who consume high amounts of antioxidant vitamins through diet or supplements, or those with high concentrations of these nutrients in their blood, tend to have lower risks of CVD. In the case of the former, however, laboratory findings may not have relevance to free-living humans. Observational epidemiologic studies cannot exclude the possibility that people who consume antioxidant-rich diets or who take vitamin supplements also share other lifestyle or dietary practices that actually account for their lower disease rates. Because of these uncertainties, the only way to determine reliably whether antioxidants play any role in reducing the risk of CVD is to conduct large-scale, randomized trials of these agents, in which adequate doses of antioxidant vitamins are tested for a sufficient duration to allow for any benefits to emerge. Several large-scale trials are now ongoing in both primary and secondary prevention. The results of these trials over the next several years should provide reliable evidence for this promising, but as yet unproven, hypothesis.