Altitude illness is a broad category of disease encompassing acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE) that can affect persons who travel to altitude without adequate acclimatization. Initial symptoms of AMS and the more serious HACE or HAPE can be subtle, and it is important that the practitioner be able to recognize and differentiate between these diagnoses because they can progress rapidly and be fatal if untreated. There are well-established criteria and many proven therapies both for prophylaxis and treatment of altitude illness; however, despite intense research efforts, the specific mechanisms of these complex diseases remain elusive. Adequate acclimatization via controlled ascent remains the most important factor in preventing altitude illness, although prophylactic pharmacotherapy also may be useful. Rapid descent remains the most important treatment factor, although treatment at altitude with various therapies is possible for mild cases with adequate resources.