SUMMARY This paper will review the function of the lung at high altitude in humans. As the first interface between the environment and the body, the lung serves a vital role in the transfer of oxygen from the air to the blood. I will describe the limits of response and adaptation of the lung to this hypoxic stress, both at rest and during exercise when oxygen and carbon dioxide flux from the tissues is greater. First, ventilation will be described in terms of the hypoxic stimulus that causes an increase in breathing (ventilatory drives) and the metabolic cost from the respiratory muscles incurred by this increase. Individuals at high altitude also have a substantial sense of dyspnea which, in and of itself, may limit exercise tolerance. The final function of the lung is to exchange oxygen and carbon dioxide, which it does at the alveolar–capillary interface. Here, important limitations are encountered because the driving pressure for oxygen from the air to the blood is lower and the more rapid transit time of blood across the pulmonary capillary allows less time for equilibration of oxygen with the blood. Both these phenomena lead to a limitation of diffusion of oxygen across the alveolar–capillary membrane and, thus, more accentuated hypoxemia. In spite of these restrictions, humans still do remarkably well in times of great stress from the hypoxic environment.