More than 80 years after the discovery of the essentiality of vitamin E for mammals, the molecular basis of its action is still an enigma. From the eight different forms of vitamin E, only α-tocopherol is retained in the body. This is in part due to the specific selection of RRR-α-tocopherol by the α-tocopherol transfer protein and in part by its low rate of degradation and elimination compared with the other vitamers. Since the tocopherols have comparable antioxidant properties and some tocotrienols are even more effective in scavenging radicals, the antioxidant capacity cannot be the explanation for its essentiality, at least not the only one. In the last decade, a high number of so-called novel functions of almost all forms of vitamin E have been described, including regulation of cellular signalling and gene expression. α-Tocopherol appears to be most involved in gene regulation, whereas γ-tocopherol appears to be highly effective in preventing cancer-related processes. Tocotrienols appear to be effective in amelioration of neurodegeneration. Most of the novel functions of individual forms of vitamin E have been demonstrated in vitro only and require in vivo confirmation. The distinct bioactivities of the various vitamers are discussed, considering their metabolism and the potential functions of metabolites.