Alpha-tocopherol transfer protein (α-TTP) is a liver cytosolic transport protein that faciliates α-tocopherol (α-T) transfer into liver secreted plasma lipoproteins. Genetic defects in α-TTP, like dietary vitamin E deficiency, are associated with infertility, muscular weakness and neurological disorders. Both human and α-TTP deficient (α-TTP^-/-) mice exhibit severe plasma and tissue vitamin E deficiency that can be attenuated by sufficient dietary α-T supplementations. In this review, we summarize the literature concerning studies utilizing the α-TTP^-/- mice. Levels of vitamin E in the α-TTP^-/- mice do not appear to be directly related to the amounts of dietary α-T or to the levels of α-TTP protein in tissues. The α-TTP^-/- mice appear to present a good model for investigating the specific role of α-T in tissue vitamin E metabolism. Furthermore, α-TTP^-/- mice appear to be useful to elucidate functions of α-TTP beyond its well recognized functions of transferring α-T from liver to plasma lipoprotein fractions.