Mechanical ventilation practices in patients with acute respiratory distress syndrome (ARDS) have progressed with a growing understanding of the disease pathophysiology. Paramount to the care of affected patients is the delivery of lung-protective mechanical ventilation which prioritizes tidal volume and plateau pressure limitation. Lung protection can probably be further enhanced by scaling target tidal volumes to the specific respiratory mechanics of individual patients. The best procedure for selecting optimal positive end-expiratory pressure (PEEP) in ARDS remains uncertain; several relevant issues must be considered when selecting PEEP, particularly lung recruitability. Noninvasive ventilation must be used with caution in ARDS as excessively high respiratory drive can further exacerbate lung injury; newer modes of delivery offer promising approaches in hypoxemic respiratory failure. Airway pressure release ventilation offers an alternative approach to maximize lung recruitment and oxygenation, but clinical trials have not demonstrated a survival benefit of this mode over conventional ventilation strategies. Rescue therapy with high-frequency oscillatory ventilation is an important option in refractory hypoxemia. Despite a disappointing lack of benefit (and possible harm) in patients with moderate or severe ARDS, possibly due to lung hyperdistention and right ventricular dysfunction, high-frequency oscillation may improve outcome in patients with very severe hypoxemia.