The presence and activity of vitamin E in the organism as well as its role in disease prevention depend, as for any other microconstituent in food, on a number of factors related to its release from the food matrix, extent of absorption, and metabolic fate. Biotransformation can be defined as the sum of processes in which vitamin E compounds are altered by the body. It involves the bioactivation and production of reactive metabolites, a series of processes generally referred to as "vitamin E metabolism." This chapter will provide an overview of the known and less known steps of vitamin E biotransformation in humans. Due to recent advances related to the biological activities and metabolic processing of vitamin E compounds, particular attention will be given to the description of the formation, identification, and functions of vitamin E metabolites. The hypothesis of a transformation-dependent bioactivation of vitamin E represents an intriguing and emerging aspect of research that deserves further investigation.