For most passengers, even those with respiratory disease, air travel is safe and comfortable. Some travelers may experience hypoxia at sea level but may not need supplemental oxygen during air travel in a hypobaric hypoxic environment. For some individuals compensatory pulmonary mechanisms may be inadequate, causing profound hypoxia. In addition, venous thromboembolism/pulmonary emboli may occur, especially during long haul flights. With adequate screening, patients at risk can be identified, therapeutic solutions can be proposed for the flight, and most can travel can continue safely with supplemental oxygen and other preventive measures.