HFOV is a mode of ventilation that can achieve oxygenation and ventilation while maintaining maximal lung recruitment on the deflation limb of its pressure-volume curve. The primary theoretical advantages of HFOV over CMV in the management of acute lung injury are that HFOV allows adequate alveolar ventilation with minimal peak-trough pressure changes, provides lung recruitment, and avoids end-inspiratory overdistension of the relatively compliant nondependent lung. Taken together, the results of studies in animals, preterm and term neonates, and older pediatric patients reveal that an "open-lung" strategy, with the goal of a high end-expiratory lung volume, is safe and superior to CMV in both the short-term (rapidly improved oxygenation and/or ventilation) and longer-term (lower incidence of chronic lung disease). The improved longer-term clinical outcomes on HFOV are presumably because of less ventilator-induced lung injury. As experience with HFOV in older patients grows, ventilator technology matures, and understanding of the pathophysiology of acute respiratory distress syndrome (RDS) deepens, it is likely that HFOV will find widespread use for the management of respiratory failure caused by acute lung injury in patients from preterm neonates to adults.