The public's faith in vitamin E, and in antioxidants generally, reflects the strong belief of scientists and health professionals in the theory that exogenous antioxidants prevent chronic diseases. Ten years have passed since publication of the first large trial showing that vitamin E supplementation had no effect in preventing cancer and cardiovascular disease (9), and subsequent trials have repeatedly confirmed this result. The story is similar for other presumed antioxidants, such as β-carotene and vitamin C. Yet the notion that consumption of antioxidants in diet and supplements can prevent disease appears to have drawn strength, rather than been weakened, by contrary results from clinical trials. Investigators have called attention to isolated findings of possible antioxidant benefits for subgroups of trial participants, or for secondary end points, when the overall results of a trial were clearly null. After β-carotene, initially viewed as an extremely potent antioxidant, was shown to be harmful in clinical trials (9–10), some scientists opined that the result represented a pro-oxidant property of the agent under certain conditions; thus, they made the seemingly perverse outcome fit the antioxidant theory. Meanwhile, research based on the antioxidant theory continues apace; a recent search of the 2004 National Institutes of Health funding database produced more than 700 hits for the term antioxidant. Most funded studies are basic research, but they include many clinical trials testing vitamin E supplements in tens of thousands of patients, with dosages ranging from 400 to 2000 IU/d, for prevention of a variety of conditions such as dementia, heart disease, and prostate cancer. These research projects have all passed a rigorous peer review, and I do not question the scientific merit of any one of them. But isn't it past the time for the scientific and public health communities to loosen their ties to a theory that lacks predictive ability for human disease?