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