At the present time, commercial aircraft cabins are required to be pressurized to the equivalent of 8,000 feet or less. Although in-flight medical emergencies are infrequent, some adults with pulmonary disease may experience significant physiological stress, exacerbation of their underlying illness, and severe hypoxemia during air travel. A careful preflight medical evaluation is essential to determine which patients with pulmonary disease can fly safely, which patients require supplemental oxygen, and which patients should not fly at all. All adults with pulmonary disease who have a preflight arterial oxygen tension of less than 70 mm Hg or a preflight pulse oximetry saturation of less than 92% should receive supplemental oxygen during air travel. The hypoxia altitude simulation test and the 6-minute walk test are useful when additional evaluation for supplemental in-flight oxygen is needed. Patients with an unstable condition, an acute exacerbation of their pulmonary disease, severe pulmonary hypertension (Class III and Class IV), or an active pneumothorax should not fly.