A review is made on the different treatment strategies essayed to date in the management of chronic mountain sickness (CMS). After a brief presentation of the epidemiology and of the pathophysiological mechanisms proposed for explaining the disease, the advantages and drawbacks of the different treatment approaches are discussed, along with their pathopysiological rationale. A particular emphasis is dedicated to the scientific foundations underlying the development of acetazolamide and angiotensin-converting enzyme inhibitors as promising therapeutic agents for CMS, as well as the clinical evidence existing so far on their usefulness in the treatment of CMS. Various methodological issues that need to be addressed in future clinical studies on efficacy of therapies for CMS are discussed. There is also a brief discussion on potential treatment options for chronic high altitude pulmonary hypertension. Closing remarks on the need of taking increasingly into account the development and implementation of preventive measures are made.