The combination of a tendency to affect otherwise fit and healthy individuals, and a characteristically rapid progression to death within hours of the first symptoms, renders high altitude pulmonary edema (HAPE) a particularly devastating illness in travelers to high altitudes. The alveolar edema and ventilation:perfusion mismatch initiate a catastrophic downward spiral of worsening alveolar hypoxia. This reviewo discusses the rationale for the use of phosphodiesterase (PDE)5 inhibitors in HAPE, compares the pharmacokinetic properties of the available agents, and appraises the relevant experimental evidence. Although this class of drugs shows promise in high altitude medicine, further research is necessary to determine the efficacy and safety of PDE5 inhibitors as a treatment for established