It has long been known that dietary amino acid adequacy is markedly influenced by energy balance but in recent years the importance of this has been generally underestimated. Important practical issues include unintentional variation in energy intake and consequence energy balance that may be responsible for much of the apparent variability in protein requirements. Because variation in energy expenditure and intakes in subjects in energy balance may influence nitrogen balance (NB), a framework for evaluating studies of protein or amino acid adequacy in relation to the level of energy intake needs definition. The common assumption that the type of energy influences protein utilization is probably incorrect with fat as effective as carbohydrate in maintaining NB at energy maintenance. A more difficult conceptual issue relates to the use of protein:energy (P:E) ratios in evaluating adequacy of intakes in relation to requirements. This is necessary given that protein intakes are determined by overall food energy intake that varies markedly throughout the life cycle and with lifestyle. For any diet that might be considered limiting in protein, population groups most likely to be at risk are those with the lowest energy requirements, the sedentary elderly. Thus, increased amino acid density of diets becomes more important for this population, and increased physical activity and higher food intakes at energy balance are likely to reduce the extent of any deficiency. Modeling of the implications of proposed protein and amino acid requirement values for likely risk of deficiency by comparing P:E ratios of intakes and requirements implies high levels of deficiency risk in both developing and developed population groups. This raises the question of whether proposed values for the lysine requirement need to be revaluated and consideration given to the extent to which adaptive mechanisms might enable the metabolic requirement for protein to be met from current intakes. J. Nutr. 134: 1588S-1596S, 2004.