Provision of adequate nutrition is recognized as a therapeutic necessity to maintain inspiratory muscle strength and prevent weaning failures in patients with acute respiratory failure requiring mechanical ventilation. Total caloric needs are empirically estimated by calculation of basal energy expenditure and modified by correction factors for concurrent levels of stress. Energy requirements can vary considerably from empiric estimations and may be better defined by indirect calorimetry that measures oxygen consumption and carbon dioxide production. Protein constituents are initiated empirically until patient-specific urea nitrogen excretion is available. The addition of fat emulsion as 20-50 percent of total daily calories limits lipogenesis, prevents excessive carbon dioxide production, and provides a volume-concentrated caloric source to fluid-restricted patients. Manipulation of nutrient composition can improve or impair ventilatory weaning and nutritional rehabilitation. The significance of substrate utilization is reviewed and recommendations for establishing nutritional regimens for mechanically ventilated adults with acute respiratory failure are provided.