Positive end expiratory pressure (PEEP) may prevent cyclic opening and collapsing alveoli in acute respiratory distress syndrome (ARDS) patients, but it may play a role also in general anesthesia. This review is organized in two sections. The first one reports the pathophysiological effect of PEEP on thoracic pressure and hemodynamic and cerebral perfusion pressure. The second section summarizes the knowledge and evidence of the use of PEEP in general anesthesia and intensive care. More specifically, for intensive care this review refers to ARDS and traumatic brain injured patients.