The term respiratory failure implies the inability to maintain either the normal delivery of oxygen to tissues or the normal removal of carbon dioxide from the tissues. There are actually three processes involved: the transfer of oxygen across the alveolus, the transport of tissues (by cardiac output), and the removal of carbon dioxide from the blood into the alveolus with subsequent exhalation into the environment. Failure of any step in this process can lead to respiratory failure. An overview of the normal physiology of pulmonary gas exchange and the pathophysiology of respiratory failure is presented in this article.