Acute lung injury and acute respiratory distress syndrome are associated with significant morbidity and mortality in critically ill patients. Although lung protective mechanical ventilation is the only therapy shown to reduce mortality and development of organ failure, several biologic pathways have been identified and provided an opportunity for therapeutic interventions. No pharmacologic or adjunctive treatments are available. Clinical studies demonstrated that prone position results in significant and clinically relevant improvement in oxygenation and ventilation, which persist when patients are returned to supine position; the beneficial response is not limited to patients turned early in disease course. Few complications are associated with prone ventilation. Clinical experience suggests that prone ventilation may protect the lung from potential detrimental effects of mechanical ventilation. Further studies are needed.