Smoke inhalation injuries are the leading cause of fatalities from burn injury. The major forms of inhalation injuries are carbon monoxide toxicity, injury to the upper airway, and pulmonary parenchymal damage. The compromised airway is protected by tracheal intubation, and respiratory failure is treated with assisted ventilation. Maintenance of good pulmonary hygiene, optomized fluid resuscitation, and routine invasive hemodynamic monitoring are the mainstays of therapy. The development of acute pulmonary insufficiency, pulmonary edema, or bronchopneumonia requires a comprehensive approach to all aspects of the illness. Acute pathophysiologic responses to inhalation injury are complex. Future therapies will target improved ventilatory strategies and the redundant host inflammatory response.