Although a role for vitamin A in immunity to infectious diseases has long been suggested, only in the last decade have epidemiological, immunologic, and molecular studies yielded substantial evidence for a central role. The recent discovery of retinoic acid and retinoid X receptors has provided a molecular basis for the action of vitamin A and its metabolites at the level of gene activation. At least a dozen clinical trials have now demonstrated that vitamin A supplementation reduces severe morbidity and mortality from infectious diseases among children who have acute measles or who are from areas in which vitamin A deficiency is endemic. Vitamin A deficiency is an immunodeficiency disorder characterized by widespread alterations in immunity, including pathological alterations in mucosal surfaces, impaired antibody responses to challenge with protein antigens, changes in lymphocyte subpopulations, and altered T- and B-cell function. Vitamin A and its metabolites are immune enhancers that have been shown to potentiate antibody responses to T cell-dependent antigens, increase lymphocyte proliferation responses to antigens and mitogens, inhibit apoptosis, and restore the integrity and function of mucosal surfaces. Vitamin A and related retinoids may have potential applications in therapy for some infectious diseases.