Most clinical trials on antioxidants using vitamin E or beta-carotene have failed to note any significant change in cardiovascular endpoints. The results of these studies have been interpreted as a setback for the oxidation hypothesis. An analysis of the hypothesis and the trials, however, points out major misconceptions about the hypothesis and unjustified outcome expectations. Wrong selection of patient population, endpoints that are incompatible with the hypothesis, poor choice of antioxidants, and lack of inclusion of biochemical markers of oxidative stress and markers of vascular response are some of the contributors to the "failure" of these trials.