Severe burn injury is followed by a profound hypermetabolic response that persists up to 24 months after injury. It is mediated by up to 50-fold elevations in plasma catecholamines, cortisol, and inflammatory cells that lead to whole-body catabolism, elevated resting energy expenditures, and multiorgan dysfunction. All of these metabolic and physiologic derangements prevent full rehabilitation and acclimatization of burn survivors back into society. Modulation of the response by early excision and grafting of burn wounds, thermoregulation, early and continuous enteral feeding with high-protein high-carbohydrate feedings, and pharmacologic treatments have markedly decreased morbidity.