One-lung ventilation (OLV) for thoracic surgery still poses a challenge for the anesthesiologist. The presence of atelectasis not only increases the risk of intraoperative hypoxemia but also favors the inhomogeneity of ventilation during OLV, which in turn can increase the forces applied to the lung parenchyma. Those forces increase the likelihood of ventilator-induced lung injury (VILI) affecting also previously noninjured lungs. In this chapter, we will review the mechanisms of VILI, and explore the basic concepts of so-called protective ventilation during OLV for thoracic surgery, with emphasis on the maintenance of adequate gas exchange while avoiding injury that might increase the risk of postoperative pulmonary complications.