The thoracic surgical patient is at special risk for increased postoperative pulmonary complications, such as atelectasis, impaired lung function and pneumonia, as well as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) with high mortality after lung resections. One-lung ventilation (OLV) induces proinflammatory responses especially in the ventilated lung, based on mechanical stress, persistent hyperperfusion, increased gas content and ventilation to perfusion mismatching. ALI may occur, even in previously healthy lungs. Ventilation management can cause and exacerbate but also attenuate ALI after OLV. Protective ventilatory approaches can improve the outcome by minimizing lung damage. However, ventilation with lower tidal volumes during OLV does not completely abolish alveolar inflammation. The present review addresses the effects of OLV and their role in ventilator-induced lung injury. Lung protective strategies to one-lung ventilation that additionally include reduction of cyclic alveolar recruitment, PEEP ventilation, limitation of inspired oxygen and pharmacological preconditioning by volatile anesthetics are discussed.