Almost a century ago, plant extracts were documented to be critical for the fertility of rodents. This activity was later ascribed to vitamin E, a term comprising a number of structurally related plant lipids that function as fat soluble antioxidants. The alpha-tocopherol transfer protein (TTP) is a critical regulator of vitamin E status that stimulates the movement of vitamin E between membrane vesicles in vitro and facilitates the secretion of tocopherol from hepatocytes. Heritable mutations in the ttpA gene cause ataxia with vitamin E deficiency (AVED), an autosomal recessive disorder characterized by low plasma vitamin E levels and progressive neurodegeneration. This chapter summarizes recent advances in our understanding of the molecular and physiological aspects of TTP activity.