Headache is known to be the predominant symptom in acute mountain sickness which is also frequently accompanied by nausea, vomiting and insomnia. Nowadays, every year millions of skiers and mountaineers are attracted to mountains all over the world. At altitudes between 2500 m and 5000 m about 20% to 90% of those who are not adapted to high altitude will experience high altitude headache (HAH). It is well documented that HAH can be best prevented by observance of the golden rule: not to go too high too fast. Although many mountaineers are aware of this rule, its observance is complicated by unknown individual susceptibility, the location of mountain huts, the use of cable cars, limited holiday time, unfavorable weather or avalanche conditions. Therefore, there is a widespread use of drugs for the treatment and prevention of HAH. In the past, the increase in cerebral blood flow during acute hypoxia was thought to be the main cause of HAH. More recent findings, however, have caused this hypothesis to be reduced in importance and have supported the pathogenetic consequence of sensitization of intracranial pain-sensitive structures. The effectiveness of cyclooxygenase inhibition for the treatment and prevention of HAH suggests that especially prostaglandins may be an important mediator between hypoxia and HAH. Besides oxygen, acetazolamide, dexamethasone and especially inhibitors of prostaglandin synthesis such as ibuprofen and naproxen are approved for the treatment of HAH. Acetazolamide, dexamethasone, and aspirin were also found to prevent HAH. The most beneficial effects however, may be achieved by the combined application of acetazolamide and aspirin. This combination increases oxygenation and reduces prostaglandin synthesis.