The evolution of respiratory care on patients with acute respiratory distress syndrome (ARDS) has been focused on preventing the deleterious effects of mechanical ventilation, termed ventilator-induced lung injury (VILI). Currently, reduced tidal volume is the standard of ventilatory care for patients with ARDS. The current focus, however, has shifted to the proper setting of positive end-expiratory pressure (PEEP). The whole lung pressure-volume (P/V) curve has been used to individualize setting proper PEEP in patients with ARDS, although the physiologic interpretation of the curve remains under debate. The purpose of this review is to present the pros and cons of using P/V curves to set PEEP in patients with ARDS. A systematic analysis of recent and relevant literature was conducted. It has been hypothesized that proper PEEP can be determined by identifying P/V curve inflection points. Acquiring a dynamic curve presents the key to the curve's bedside application. The lower inflection point of the inflation limb has been shown to be the point of massive alveolar recruitment and therefore an option for setting PEEP. However, it is becoming widely accepted that the upper inflection point (UIP) of the deflation limb of the P/V curve represents the point of optimal PEEP. New methods used to identify optimal PEEP, including tomography and active compliance measurements, are currently being investigated. In conclusion, we believe that the most promising method for determining proper PEEP settings is use of the UIP of the deflation limb. However, tomography and dynamic compliance may offer superior bedside availability.