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Vitamin A deficiency is one of the most common nutrient deficiency syndromes in children from developing countries. It is also correlated with the increased severity and incidence of certain infections. Until recently, vitamin A research was focused on preventing xerophthalmia and blindness in Third World Countries and on the development of synthetic retinoid molecules, with lower toxicity than vitamin A, for the treatment of skin diseases. However, there has been a major shift of emphasis in the last five to ten years. There is a risk of death from xerophthalmia, primarily from complications with infectious diseases. Intermittent treatment with the very large doses of vitamin A prescribed to combat blindness was shown to be effective. This suggests that vitamin A may affect specific elements of the immune system. High-dose vitamin A supplements have been given, at widely-spaced time intervals, to preschool children in communities where vitamin A deficiency causes xerophthalmia and blindness, over the last 20 to 30 years. A strong correlation between mortality and xerophthalmia was identified. Death then became the principal outcome measured because it was easier to detect than xerophthalmia, particularly in large clinical trials in high risk regions where clinical expertise was minimal and vitamin A deficiency was a commoner cause of death than blindness. Other, food-based approaches to the treatment and prevention of vitamin A deficiency, involving foods naturally rich in retinol or carotenoid, or foods artificially fortified with these nutrients, should be developed.