Some studies have suggested that antioxidant supplements may prevent cancer or reduce cancer mortality; however, the data are not definitive. The results of 2 large clinical trials that assessed the effects of antioxidant supplementation on cancer in men are reported in this issue. In the first article, Lippman and colleagues Article report results from the Selenium and Vitamin E Cancer Prevention Trial, in which men aged 50 years or older were randomly assigned to 4 treatments: selenium, vitamin E, selenium plus vitamin E, or placebo. After a median follow-up of 5.46 years (range, 4.17-7.33 years), the investigators found that selenium or vitamin E, alone or in combination, did not prevent prostate cancer. In the second article, which is based on an analysis of data from the Physicians' Health Study II, Gaziano and colleagues Article report that compared with placebo, neither vitamin E nor vitamin C supplementation reduced the risk of prostate or total cancer during a mean follow-up of 8.0 years. In an editorial, Gann Article discusses lessons learned in clinical trials of nutritional prevention of prostate cancer.