During the last decade, major advances in the understanding of the mechanism of high altitude pulmonary edema (HAPE) have supplemented the landmark work done in the previous 30 years. A brief review of the earlier studies will be described, which will then be followed by a more complete treatise on the subsequent research, which has elucidated the role of accentuated pulmonary hypertension in the development of HAPE. Vasoactive mediators, such as nitric oxide (NO) and endothelin-1, have played a major role in this understanding and have led to preventive and therapeutic interventions. Additionally, the role of the alveolar epithelium and the Na-K ATPase pump in alveolar fluid clearance has also more recently been understood. Direction for future work will be given as well.