The provision of optimal nutritional care is based on accurate estimations of patients’ resting energy expenditure. The latter can be calculated with the use of predictive equations or measured with indirect calorimetry (IC). Owing to their ease of use, mathematical equations have largely replaced IC in clinical practice. This article examines the limitations and predictive inaccuracy of commonly used equations in pediatrics, which may contribute to the provision of poor nutritional care and directly affect patient outcomes. In addition, the role of IC is discussed and the physiology of nutrient metabolism, in terms of energy expenditure, is reviewed.