Acute respiratory distress syndrome (ARDS) is a severe form of respiratory failure that is characterized by marked hypoxemia, bilateral infiltrates on chest radiograph, and no clinical evidence of left ventricular failure. Mechanical ventilation with positive end-expiratory pressure (PEEP) is a cornerstone therapy for ARDS patients. Because the fundamental aim of supportive treatment is to improve arterial oxygenation, several alternatives to mechanical ventilation with PEEP have been used. One of these alternative therapies is prone positioning, which has been used safely to improve oxygenation in many patients with ARDS. Despite encouraging results, however, the use of prone positioning is not widely accepted as an adjunct to therapy in hypoxemic patients because, aside from temporarily improving gas exchange, it does not seem to affect the outcome of these patients. This article reviews the rationale for using prone positioning in ARDS patients who require intubation and mechanical ventilation.