People are visiting high-altitude environments with increasing frequency, resulting in increased incidence of high-altitude illness. Hypoxia, the primary insult to the human body in high altitudes, dramatically alters human physiology, metabolism, and anatomy. Humans’ delicate physiological balance is susceptible to disruption leading to high-altitude pathologies, including acute mountain sickness, high-altitude cerebral edema, and high-altitude pulmonary edema. Acute mountain sickness anchors the benign end of a spectrum of high-altitude illnesses. At the most life-threatening end is high-altitude cerebral edema. However, it is high-altitude pulmonary edema that has the highest rate of death among high-altitude patients. There are many temporizing treatments available, but descent is the definitive solution. Many options must be considered as an EMS medial director or EMS physician, but preparation through education and training to adequately prevent and treat altitude illnesses, should they occur, are of paramount importance.