Fetal life conditions the responses of a newborn infant to high altitude. The fetal circulation is characterized by high pulmonary vascular resistance and low pulmonary blood flow, as well as intra and extracardiac shunts that serve to route blood to and from the placenta and around the fetal lungs. At birth, rapid changes occur in the pulmonary circulation under normoxia; pulmonary vascular resistance falls, pulmonary blood flow increases dramatically, and the fetal shunts close functionally, then anatomically. Under conditions of hypoxia, the changes of circulatory transition occur more slowly, and pronounced hypoxia can cause a reversion to fetal circulatory patterns, albeit without the placenta to serve as the organ of oxygenation. Underlying medical conditions of newborn infants that combine exaggerated hypoxemia in response to high altitude hypoxia with an underlying predisposition to pulmonary hypertension can increase the likelihood of problems at high altitude. Awareness of risk factors and clinical signs of hypoxemia in newborn infants, as well as measurement of arterial oxygen saturation by pulse oximetry, can aid health professionals and parents in recognizing and preventing altitude-associated illness.