The tremendous variability in resting energy expenditure makes efforts to predict caloric requirements difficult. Indirect calorimetry has provided a valuable tool in assessing energy expenditure, evaluating the way in which the body uses nutrient fuel, and designing nutritional regimens that best fit the clinical condition of the patient. The many indirect calorimetric instruments available vary in their application to clinical nutrition. The best metabolic studies are achieved by controlling the testing environment, accounting for the many clinical factors that may affect measurements, and eliminating potential sources for error. Although indirect calorimetry would seem to reduce the likelihood of complications from overfeeding, its greatest effect may be in cost savings by avoiding unnecessary nutritional support and in providing a means for clinical research.