Over 150 million people, including many children, live at high altitude (>2500m) with the majority residing in Asia and South America. With increases in elevation the partial pressure of oxygen (pO2) is reduced, resulting in a hypobaric hypoxic environment. Fortunately, humans have evolved adaptive processes which serve to acclimate the body to such conditions. These mechanisms, occurring along a specific time course, result in tachypnea, tachycardia, diuresis, hematopoiesis, and a shift in the oxygen dissociation curve favoring an increased affinity for oxygen. These, along with other physiological effects, including increased pulmonary vascular resistance, alterations in cerebral blood flow and changes in sensitivity to opioids, must be considered when administering anesthesia at high altitudes. Susceptible individuals or those who ascend too quickly may outpace the body’s ability to acclimate resulting in one or more forms of high-altitude sickness ranging from the milder Acute Mountain Sickness to the more serious conditions of High-Altitude Pulmonary Edema and Cerebral Edema, either of which can be life-threatening if not promptly recognized and treated. Since the adaptive mechanisms for acclimatization greatly affect the cardiopulmonary systems, patients with underlying health issues such as sleep apnea, congenital heart disease, and asthma may have susceptibilities and warrant special consideration. Clinicians should have an understanding of the physiologic adaptations, anesthetic considerations, and special concerns in these populations in order to offer the best care possible.