The density of helium is markedly lower than that of air or any of its components, leading to a substantial decrease in airway resistance to flow when it is inhaled. In mechanically ventilated patients with obstructive airway disease, replacing the usual air–oxygen mixture with helium–oxygen has been shown to reduce dynamic hyperinflation and intrinsic positive end-expiratory pressure; to decrease lung inflation pressures, respiratory acidosis, and work of breathing; and to improve arterial blood gases. Aerosol delivery to distal airways is enhanced with helium–oxygen. Preliminary data also suggest that the use of helium–oxygen could be a valuable approach to decrease postextubation respiratory distress. However, interference with ventilator function and added costs are two major disadvantages of helium–oxygen. Hence, before its widespread use in mechanically ventilated patients can be recommended, studies are needed to determine whether these favorable short-term effects can influence patient outcome.