Vitamin E is one of the most abundant lipid-soluble antioxidant agents found in plasma and cells of higher mammals. The uptake, transport and tissue delivery of alpha-tocopherol, a key vitamin E form, involves molecular, biochemical, and cellular processes closely related to overall lipid and lipoprotein homeostasis. This review highlights recent findings that have led to a better understanding of vitamin E transport, including intestinal absorption, hepatic transport, and cellular uptake of alpha-tocopherol in vivo. This new information may be critical for manipulation of vitamin E homeostasis in a variety of oxidative stress-related disease conditions in humans.