The foundation of mechanical ventilation for acute respiratory distress syndrome involves limiting lung overdistention by using small tidal volumes or transpulmonary pressures. Potential for additional lung recruitment with higher positive end-expiratory pressure (PEEP) should be assessed. When stress index indicates tidal recruitment-derecruitment, PEEP is increased to higher values. Alternatively, a high PEEP table is used in all patients. When these conventional approaches are insufficient to sustain acceptable gas exchange, rescue is attempted using extracorporeal therapies, airway pressure-release ventilation, inhaled vasodilators, or high-frequency oscillatory ventilation. An integrated approach takes into account acute respiratory distress syndrome severity, the potential for recruitment with PEEP, and the response to initial ventilator choices.