Arterial blood gas analysis is used to evaluate oxygen and carbon dioxide gas exchange and acid-base status. Few studies identify indications for arterial blood gas analysis, especially with regard to optimizing the quality of patient care. General indications in severely ill adults usually include pathophysiologic abnormalities that can alter gas exchange or acid-base disturbances. Most commonly identified general indications have not been prospectively studied to determine if this analysis is necessary for diagnosis or management. Clinical settings where analysis is indicated involve patients with acute asthma in the emergency room, postoperative treatment of patients who have had coronary artery bypass graft surgery, stable patients in the intensive care unit, and patients receiving prophylactic supplemental low-flow oxygen by nasal cannula. Advances in noninvasive monitoring have suggested other possible clinical settings. However, further prospective, controlled clinical studies are needed to establish indications for arterial blood gas analysis and the role of noninvasive monitoring.