Multiple animal and human studies have shown that prone positioning improves oxygenation and reduces ventilator-induced lung injury (VILI) in the setting of acute lung injury or acute respiratory distress syndrome (ARDS). In this article, the physiologic changes explaining the improvement in oxygenation are reviewed, how prone positioning reduces VILI is described, randomized controlled trials of prone ventilation in patients with ARDS are evaluated, the complications associated with prone ventilation are summarized, suggestions are made as to how these might be reduced or avoided, and when prone ventilation should start and stop and for what duration it should be used are discussed.