An in-flight medical emergency (IME) refers to any medical incident on board a commercial airline that has exceeded the handling ability of the flight crew. IMEs are more common than we tend to think, occurring roughly every 600 flights, and the incidence is expected to rise considerably due to increases in air traffic, flight times, and the proportion of elderly, co-morbid passengers. Physicians on board are often called upon to assist affected passengers, but most are unaware of the unique aspects of the cabin atmosphere, the resources available to them, and the policies guiding intervention in this complex, resource-limited environment. While anesthesiologists are often viewed through the lens of perioperative care, our expertise with respect to physiology, critical care, and crisis management renders us particularly useful to passengers during an IME.