Protective ventilation includes a strategy with low tidal volume, Plateau pressure, driving pressure, positive endexpiratory pressure (PEEP), and recruitment maneuvers on the ventilated lung. The rationale for the application of PEEP during one-lung ventilation (OLV) is that PEEP may contribute to minimize atelectrauma, preventing airway closure and alveolar collapse and improving the ventilation/perfusion to the ventilated lung. However, in case of high partial pressure of oxygen the application of PEEP may cause increased pulmonary vascular resistance, thus diverting blood flow to the nonventilated lung, and worsening ventilation/perfusion. Further, PEEP may be associated with higher risk of hemodynamic impairment, increased need for fluids and vasoactive drugs. Positive effects on outcome have been reported by titrating PEEP according to driving pressure, targeted to obtain the optimum respiratory as well as pulmonary system compliance. This may vary according to the method employed for titration and should be performed individually for each patient. In summary, the potential for harm combined with the lack of evidence for improved outcome suggest that PEEP must be judiciously used during OLV even when titrated to a safe target, and only as much as necessary to maintain an appropriate gas exchange under low protective tidal volumes and driving pressures.