The safety of large doses of vitamin E went virtually unquestioned until the early 2000s, when several studies were published showing that consumption of vitamin E from dietary supplements increased mortality, as well as the risk of gastrointestinal cancer and heart failure. These studies prompted numerous letters to the editors of medical journals and widespread coverage in the media. Both the medical community and the general public became confused and concerned about the use of vitamin E supplements. The purpose of this article is to review the medical literature and to explain these unusual findings. First we provide an overview of the earlier literature on vitamin E. Second, we provide a critical assessment of three meta-analyses that were neutral or negative toward vitamin E supplementation. Third, we review the limitations of meta-analyses in general. Fourth, we assess the individual studies that comprised one of the three meta-analyses. Since all three meta-analyses used many of the same studies, the individual critique should further the understanding of the limitations of these meta-analyses, and the meta-analysis approach in general. Lastly, we offer some guidance for healthcare professionals to give to the general, healthy public and those with chronic conditions who are no doubt left puzzled as to what to do regarding vitamin E supplementation.