OBJECTIVE: To review clinical trials evaluating the safety and efficacy of vitamin E supplementation in Alzheimer's disease, Parkinson's disease, tardive dyskinesia, and cataract. DATA SOURCES: Using the MeSH terms alpha-tocopherol, tocopherols, vitamin E, Parkinson disease, tardive dyskinesia, Alzheimer disease, cataract, and clinical trials, a literature review was conducted to identify peer-reviewed articles in MEDLINE (1966-July 2005). STUDY SELECTION AND DATA EXTRACTION: Published materials including original research, review articles, and meta-analyses were reviewed. Only English-language articles and trials that included vitamin E alone or in combination with other vitamins or minerals were reviewed. Emphasis was placed on prospective, randomized, double-blind, placebo-controlled clinical trials. DATA SYNTHESIS: The clinical studies demonstrated contradicting results regarding the benefits of vitamin E in Parkinson's disease, tardive dyskinesia, and cataract. The study reviewed for Alzheimer's disease seemed to show benefit when vitamin E was used; however, the statistical methods employed are questionable. There is enough evidence from large, well-designed studies to discourage the use of vitamin E in Parkinson's disease, cataract, and Alzheimer's disease. We recommend that vitamin E be considered a treatment option in patients with tardive dyskinesia only if they are newly diagnosed. CONCLUSIONS: We encourage patients to supplement with vitamin E-rich foods. The use of a daily multivitamin, which usually contains 30 IU of alpha-tocopherol, may be beneficial; however, we discourage individual vitamin E supplements that usually contain 400 IU of alpha-tocopherol.