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Indirect calorimetry is the method by which metabolic rate and substrate utilization are estimated in human beings starting from respiratory gas exchange measurements and urinary nitrogen excretion. This method is based on some models and assumptions that must be known and taken into consideration to correctly interpret the results obtained. Recent advances in technology and the availability of precise and portable metabolic carts have made this technique practical at the bedside even in critically ill patients. It must be considered that, particularly in the ICU, there may be several sources of error and many technical difficulties in applying this methodology. Taking into account the relevant clinical studies related to the outcomes of critically ill patient, this article defines when the assessment of energy expenditure by indirect calorimetry may provide useful and valid information. Review of the literature suggests that the clinical application of indirect calorimetry in critically ill patients, although promising, requires further evaluation. Currently, the potential useful clinical applications of indirect calorimetry in this category of patients can be summarized as follows: (1)|assessment of energy expenditure in patients who fail to adequately respond to the estimated nutritional needs; (2)|assessment of energy expenditure in patients with single- or multiple-organ dysfunction who need prolonged ICU care and artificial nutritional support; (3)|assessment of the effects induced by artificial nutrition on the cardiocirculatory and respiratory systems in mechanically ventilated patients with acute respiratory failure; (4)|monitoring of V˙O 2 during weaning from mechanical ventilation. Nutrition 1997; 13:349-358.