Ventilatory objectives in patients with acute lung injury and acute respiratory distress syndrome include effective gas exchange and avoidance of ventilator-induced lung injury. In theory, high frequency ventilation (HFV), applied using an open lung approach, accomplishes these objectives, by maintaining end-expiratory alveolar recruitment while avoiding end-inspiratory alveolar overdistension. In addition, by optimizing alveolar recruitment and thus ventilation perfusion matching, the use of HFV may allow reductions in delivered oxygen to less toxic levels. The types of HFV in current clinical use include high frequency jet ventilation, high frequency oscillatory ventilation, and high frequency percussive ventilation. The vast majority of trials of HFV have been conducted in the neonatal population, with relatively little published information in the adult population. In this review, I will briefly discuss the mechanisms of gas exchange, describe relevant human studies evaluating HFV, and explain why early studies failed to show any benefits, whereas recent studies appear to be more promising.