Acute respiratory distress syndrome (ARDS) is a severe form of respiratory failure. It remains one of the most devastating conditions in the intensive care unit. Mechanical ventilation with positive end-expiratory pressure is a cornerstone therapy for ARDS patients. One adjuvant alternative is to place the patient in a prone position. Since it was first described in 1976, prone positioning has been safely employed to improve oxygenation in many patients with ARDS. Prone positioning may also minimize secondary lung injury induced by mechanical ventilation, although this benefit has not been investigated as extensively, despite its potential. In spite of a strong physiological justification, prone positioning is still not widely accepted as an adjunct therapy in ARDS patients and it is only used regularly in only 10% of ICUs. This may be explained in part by the reluctance to change position, risks and unclear effects on relevant outcomes. In this paper, we review all aspects of prone positioning, from the pathophysiology to the clinical studies of patient outcome, and we also discuss the latest controversies surrounding this treatment.