Patients with acute respiratory distress syndrome or acute lung injury often have a number of risk factors that increase the lung’s susceptibility to injury by mechanical ventilation and that also decrease the lung’s ability to repair the damage incurred. Mechanical ventilation may worsen lung injury by physical force as a result of regional lung overdistension or regional lung shear forces generated during receptive opening and collapse of lungs. The structural disruption caused by ventilation can lead to release of inflammatory mediators, and ventilationper semay also directly activate effector cells to release mediators, resulting in systemic inflammation. Recent clinical studies suggest that lung-protective ventilatory strategies can reduce the incidence of ventilator-induced lung injury, resulting in a decrease in mortality. Monitoring of dynamic pressure-time curve during constant inflation may help to predict and minimize ventilator-induced lung injury. Pharmacologic interventions blocking the release of mediators from effector cells and inhibiting the activity of mediators have also shown promise in animal studies.