One-lung anesthesia with its attended unique physiologic considerations provides various clinical challenges to the anesthesiologist. Hypoxemia during 1-lung anesthesia remains a major clinical problem. Although it is difficult to prescribe a single ventilation technique that is ideal for all, preoperative patient characteristics and the nature of the surgery should be taken into account to develop a safe strategy for the patient and avoid catastrophic hypoxemia. Pharmacologic agents may be used to favorably manipulate the pulmonary circulation. The importance of high vigilance and clear communication with the surgeon cannot be over emphasized.