Purpose of Review Hypoxemia during one-lung ventilation, while decreasing in frequency, persists as an intraoperative challenge for anesthesiologists. Discerning when desaturation and resultant hypoxemia correlates to tissue hypoxia is challenging in the perioperative setting and requires a thorough understanding of the physiology of oxygen delivery and tissue utilization. Recent Findings Oxygen delivery is not directly correlated with peripheral oxygen saturation in patients undergoing one-lung ventilation, emphasizing the importance of hemoglobin concentration and cardiac output in avoiding tissue hypoxia. While healthy humans can tolerate acute hypoxemia without long-term consequences, there is a paucity of evidence from patients undergoing thoracic surgery. Increasingly recognized is the potential harm of hyperoxic states, particularly in the setting of complex patients with comorbid diseases. Summary Anesthesiologists are left to determine an acceptable oxygen saturation nadir that is individualized to the patient and procedure based on an understanding of oxygen supply, demand, and the consequences of interventions.

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