One-lung ventilation (OLV) is essential for many thoracic and an increasing number of non-thoracic minimally invasive procedures. Beyond the well-recognized disturbance of ventilation-perfusion matching, recent years have seen a mounting body of evidence implicating OLV in the creation of acute lung injury. After reviewing the fundamentals of OLV physiology, this article examines the evidence for altering individual ventilatory parameters toward protective OLV.