Morbidly obese subjects are characterized by important changes in respiratory function both during spontaneous breathing as well as during general anesthesia and mechanical ventilation. The most characteristic abnormalities consist of decreased functional residual capacity (FRC), reduced expiratory reserve volume, decreased compliance and increased resistance of the respiratory system. Breathing at low lung volume promotes airway closure in the dependent lung zones with consequent gas exchange abnormalities. Furthermore, the decreased expiratory reserve as a result of decreased FRC and the higher ventilatory requirements of these patients due to increased metabolic demands may promote expiratory flow limitation (EFL) in the tidal volume range. The presence of peripheral airway closure and EFL during tidal breathing promotes peripheral airway injury and may accelerate the abnormalities of lung function. The risk of injury is expected to be higher during mechanical ventilation due to the high-pressure transients, which develop under this condition. Consequently, external positive end-expiratory pressure (PEEP) must be applied to these subjects in order to increase the end-expiratory lung volume above the closing volume as well as the flow limitation volume and thus decrease the risk of peripheral airway injury.