Advances in our knowledge about the role vitamin C, vitamin E, and beta-carotene may play in reducing the risk of chronic diseases have been derived concomitantly from several different research approaches, each with its own advantages and limitations. Evaluation of the evidence for potential health benefits of antioxidant nutrients should include the entire spectrum of available scientific evidence--from cell biology, animal studies, clinical trials, and epidemiologic surveys--and consider the quality, strength, consistency, and biological plausibility of this evidence. However, difficult questions arise when considering how strong the correlation should be between the totality of evidence and the conclusions drawn for making individual and public health recommendations. Many of these questions address the need for additional research not only directed to the efficacy and safety of these nutrients but to their bioavailability, interactions with one another and other dietary factors, mechanisms of action, and methods to assess their functional status.