During the last 50 years, the perception of nutrition variables that affect behavioral development has shifted, as have the scientific hypotheses that were addressed, the design of the studies that were conducted, the nature and composition of the dietary supplements that were given and compared and the interpretation of outcomes. Methods of diagnosing malnutrition and identifying the populations at risk of becoming malnourished are reviewed in relation to nutrition interventions. Even in dietary supplementation studies it can be difficult to isolate specific nutrient effects because of associations and interactions among dietary components. These and other problems associated with the study of possible effects of dietary energy, protein and micronutrients, and of breast vs. formula feeding on human development are examined. Where dietary intake data, biochemical indicators or clinical symptoms strongly suggest that presence of a single nutrient deficiency, the appropriate action may continue to be food supplementation or fortification, until the corresponding nutrient deficiency has been rectified in the habitual diet; where the nature of the deficiency is less clear, supplementation trials and programs aimed at improving dietary diversity and quality in general are more likely to show effects on indicators of behavioral development.