α-Tocopherol (α-T) is a required dietary nutrient for humans and thus is a vitamin. This narrative review focuses on vitamin E structures, functions, biological determinants and its deficiency symptoms in humans. The mechanisms for the preferential α-T tissue enrichment in the human body include the α-T transfer protein (TTPA) and the preferential metabolism of non-α-T forms. Potential new α-T biomarkers, pharmacokinetic data, and whether there are better approaches to evaluate and set the α-T dietary requirement are discussed. Finally, the possible role of α-T supplements in delay of chronic diseases and the evaluation of vitamin E safety are considered.