In the experimental setting, repeated derecruitments of the lungs of ARDS models accentuate lung injury during mechanical ventilation, whereas open lung concept strategies can attenuate the injury. In the clinical setting, recruitment manuevers that use a continuous positive airway pressure of 40 cmH2O for 40 secs improve oxygenation in patients with early ARDS who do not have an impairment in the chest wall. High intermittent positive end-expiratory pressure (PEEP), intermitent sighs, or high-pressure controlled ventilation improves short-term oxygenation in ARDS patients. Both conventional and electrical impedance thoracictomography studies at the clinical setting indicate that high PEEP associated with low levels of pressure control ventilation recruit the collapsed portions of the ARDS lungs and that adequate PEEP levels are necessary to keep the ARDS lungs opened allowing a more homogenous ventilation. High PEEP/low tidal volume ventilation was seen to reduce inflammatory mediators in both bronchoalveolar lavage and plasma, compared to low PEEP/high tidal volume ventilation, after 36 hours of mechanical ventilation in ARDS patients. Recruitment maneuvers that used continuous positive airway pressure levels of 35-40 cmH2O for 40 secs, with PEEP set at 2 cmH2O above the lower inflection point of the pressure-volume curve, and tidal volume < 6 mL/kg were associated with a 28-day intensive care unit survival rate of 62%. This contrasted with a survival rate of only 29% with conventional ventilation (defined as the lowest PEEP for acceptable oxygenation without hemodynamic impairment with a tidal volume of 12 mL/kg), without recruitment manuevers (number needed to treat = 3; p < 0.001). In the near future, thoracic computed tomography associated with high-performance monitoring of regional ventilation may be used at the bedside to determine the optimal mechanical ventilation of the ARDS keeping an opened lung with a homogenous ventilation.