Technical Abstract: Vitamin A was called the anti-infective vitamin early in the 20th century when vitamin A deficiency was shown to increase the severity of infections of experimental animals. Squamous metaplasia caused by vitamin A deficiency was known to disrupt the mucosal barrier to infection at that time but later insights into how vitamin A deficiency impaired vitamin A deficiency awaited the development of research methods in cellular immunology, and identification of retinoic acid as the key vitamin A metabolite active in the immune system, late in the 20th century. It is now evident from studies in rodents that vitamin A deficiency impairs many aspects of both innate and adaptive immunity, but particularly development of antibody responses to T cell-dependent antigens, secretory IgA responses at mucosal surfaces, development of T-helper cell subsets, and trafficking of lymphocytes to the intestinal tract. These defects are also presumed to occur in humans though data are quite limited. Correcting such defects is presumably responsible for the ability of vitamin A supplementation to decrease the risk of mortality from some common infections of childhood (e.g., diarrhea and measles) in infants over six months of age in developing country settings where the risk of death from such infections is high.