α-Tocopherol is the only tocopherol that has been shown to prevent the human deficiency disease Ataxia with Isolated Vitamin E Deficiency (AVED), and thus it is the only one that, for humans, can be called vitamin E. Vitamin E in addition to preventing AVED has documented immune boosting properties and an activity against nonalcoholic hepatosteatosis and low-grade inflammation. Epidemiological studies indicating that vitamin E could prevent cardiovascular events, neurodegenerative disease, macular degeneration, and cancer were in general not confirmed by clinical intervention studies. Vitamin E and some of its metabolites modulate cell signaling and gene transcription. Future research is needed to achieve a better understanding of the molecular events leading to gene regulation by vitamin E, especially in its phosphorylated form. Isolation and characterization of the vitamin E kinase and vitamin E phosphate phosphatase will help in the understanding of cell regulation processes modulated by vitamin E. A clarification of the pathogenesis of AVED remains an important goal to be achieved.