Vitamin E is essential for human health and may play a role in the prevention of some degenerative diseases. Its bioavailability, however, is wide ranging and is affected by numerous factors. Recent findings showing that the intestinal absorption of vitamin E involves proteins have raised new relevant questions about factors that can affect bioavailability. It is, therefore, opportune to present a current overview of this topic. This review begins by exploring what is known, as well as what is unknown, about the metabolization of vitamin E in the human upper gastrointestinal tract and then presents a methodical evaluation of factors assumed to affect vitamin E bioavailability. Three main conclusions can be drawn. First, the proteins ABCA1, NPC1L1, and SR-BI are implicated in the absorption of vitamin E. Second, the efficiency of vitamin E absorption is widely variable, though not accurately known (i.e., between 10% and 79%), and is affected by several dietary factors (e.g., food matrix, fat, and fat-soluble micronutrients). Finally, numerous unanswered questions remain about the metabolization of vitamin E in the intestinal lumen and about the factors affecting the efficiency of vitamin E absorption.