Numerous studies have provided evidence suggesting that aging is associated with significant adverse changes in the immune system, a phenomenon often called immunosenescence, which may be responsible for an observed increase in morbidity and mortality from infectious disease and cancer in the elderly. While a variety of immune cells are known to be affected by aging, declined T cell function is the most striking and best characterized feature of immunosenescence. Both intrinsic changes in T cells and alteration in extrinsic factors are involved. Nutritional intervention has been promoted as a promising approach to delaying/reversing immunosenescence, and vitamin E is one of the best studied candidates in this regard. While vitamin E deficiency is rarely seen, both animal and human studies suggest that intake above currently recommended levels may help restore T cell function which becomes impaired with aging. This effect of vitamin E can be accomplished by directly impacting T cells as well as indirectly, by inhibiting production of prostaglandin E2, a T cell-suppressing lipid mediator known to increase with aging. Vitamin E-induced enhancements of immune functions may have significant clinical implications since vitamin E supplementation has been shown to be associated with both enhanced resistance to influenza infection in aged mice and reduced risk of acquiring upper respiratory infections in elderly human subjects. With a focus on our own work, this paper provides an overview on the beneficial effects of increased vitamin E intake on age-related decline in T cell function, the underlying mechanisms, and its clinical application in reducing the risk of infection.