Pulmonary hyperinflation is a major medical problem in patients with advanced chronic obstructive pulmonary disease (COPD) or acute asthma. The apparent beneficial effects of pulmonary hyperinflation on lung mechanics, such as an increased airway patency and lung elastic recoil, are by far overwhelmed by the deleterious effects on the pressure generating capacity of the respiratory muscles. Moreover, the ventilatory workload can be remarkably increased: 1) by the displacement of the respiratory system toward the upper, flat portion of the pressure-volume curve; 2) by the need to expand the chest wall and not only the lungs; and 3) by the intrinsic positive end-expiratory pressure (PEEPi) systematically associated with dynamic hyperinflation. In mechanically ventilated patients, the mechanisms underlying pulmonary hyperinflation as well as its pathophysiological consequences do not differ from those described in spontaneously breathing patients. However, there are some specific issues that should be taken into account, namely the effect of the endotracheal tube and the mode and setting of the ventilator. In mechanically ventilated patients, pulmonary hyperinflation increases the risk of barotrauma and may hamper weaning due to the excessive burden of PEEPi, which can even lead to ineffective inspiratory efforts. Because of its harmful consequences, pulmonary hyperinflation must be treated aggressively by pharmacological therapy and, when needed, by ventilatory treatment. The setting of the ventilator must be predetermined to ensure the longest possible time for expiration, and positive end-expiratory pressure can be applied to prevent an excessive workload for the patient and ineffective inspiratory efforts.