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Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) describe syndromes of diffuse parenchymal lung injury resulting from a variety of inflammatory triggers. The pathophysiological consequences include stiff, low-compliance lungs with impaired gas exchange. Importantly, there is often marked heterogeneity of disease. Positive pressure ventilation must therefore not only focus on recruiting and ventilating diseased units but must also avoid injuring healthy units. To this end, the goals of mechanical ventilatory support of ALI and ARDS have shifted over the last decade to providing smaller (and thus less injurious) tidal volumes and accepting consequently lower arterial values for PaO2 and the development of respiratory acidosis. This has resulted in significant improvements in outcomes. Future developments will need to further refine this lung protective concept.