Background Vitamin A deficiency is a major public health nutrition problem, affecting an estimated 190 million preschool-aged children and 19 million pregnant and lactating women globally, and 83 million adolescents in Southeast Asia alone. Its consequences (disorders) include xerophthalmia (the leading cause of early childhood blindness), increased severity of infection, anemia, and death. Because vitamin A deficiency is largely due to chronic dietary insufficiency of preformed vitamin A and proactive carotenoids, food fortification can offer an effective approach to prevention. Objective To provide guidance on fortifying wheat and maize flour milled in industrial rollers for national fortification programs in countries where vitamin A deficiency is considered a public health problem. Methods Critical review of the literature on the dietary gap in vitamin A intake and levels of wheat flour intake among risk groups as a basis for determining vitamin A fortificant levels. Additional review of efficacy evidence, safety and cost considerations, and country experiences related to wheat-flour fortification with vitamin A. Results Mill-rolled wheat flour is a technically fortifiable, centrally processed food vehicle that, where routinely and adequately consumed by target groups, should be considered a candidate for fortification. Vitamin A can be stable in flour under typical, ambient conditions, with processing losses estimated at approximately 30%, depending on source and premix conditions. Conclusions Factors to guide a decision to fortify flour with vitamin A include the extent of deficiency, availability of other food vehicle options, the centrality of milling, market reach and population intake distributions of the flour products, the dietary vitamin A intake required, and associated costs. Large gaps persist in knowledge of these factors, which are needed to enable evidence-based fortification in most countries, leaving most decisions to fortify guided by assumptions. Where flour can and should be fortified, guidelines are given for providing nearly 25% of the Recommended Dietary Allowance for vitamin A to vulnerable groups consuming varying ranges of flour products. The costs will vary according to the level of fortification.