How should this investigation influence the management of HAPE? Tadalafil and dexamethasone offer 2 new, effective options for preventing HAPE. According to their likely mechanism of action, both should be effective in treating established HAPE. This point, nevertheless, needs to be tested, especially in the case of dexamethasone; if its protection depends on genomic changes, its onset of action may be too slow for emergent therapy. Although the reflex is often to reach for a prescription pad, physicians should counsel people traveling to high altitude, particularly those with a history of altitude intolerance, about safe ascent rates. As a useful rule, once above 3000 m, any further gain in altitude should be limited to no more than 300 to 350 m/d. If signs or symptoms suggestive of HAPE develop, the mountaineer should stop or descend. Prudent ascent rates are effective because they allow time for multiple mechanisms of adaptation at the organ and cellular level to maintain adequate tissue oxygen delivery and strengthen the pulmonary microvasculature (5). However, HAPE-susceptible individuals or rescue team members who must ascend at unsafe rates should consider prophylaxis with nifedipine, tadalafil, or dexamethasone. Taking dexamethasone for a long time while on an extended trek could lead to hyperglycemia, hypercalciuria, protein catabolism, and immune suppression. It will be interesting to see whether inhaled corticosteroids can substitute for oral dosing, which would avoid these adverse effects.