Vitamin E was discovered by Evans and Bishop in 1922. Work in the 1930s revealed the chemical structure and the biological function of alpha-tocopherol. In the 1940s Filer and others demonstrated that vitamin E protects tissue unsaturated fatty acids against oxidation. The 1940s and the 1950s marked the beginning of interest in the role of vitamin E in infant nutrition. During this period, investigators examined the intestinal absorption of vitamin E in infants and its use for the prevention of hemolysis, retrolental fibroplasia, intracranial hemorrhage, and pulmonary oxygen toxicity. These studies were the forerunners of more recent studies examining possible benefits of vitamin E therapy in premature infants. Recent studies confirmed earlier reports indicating that enteral administration of vitamin E is the safest and most effective route in infants. Although preventing vitamin E deficiency is clearly necessary, neither earlier nor more recent work has shown any benefit from high-dose vitamin E therapy (greater than 20 IU X kg-1 X d-1) for premature infants.