Pulmonary arterial hypertension (PAH) is a progressive disease without a cure. The primary treatment goal for patients with this disease is improving pulmonary blood flow through vasodilation of the pulmonary arteries. Several drugs are available that ameliorate walk distance and hemodynamics, but their maximum tolerated doses are limited in critically ill patients with PAH because of systemic vasodilation resulting in hypotension. The ideal vasodilator would be cost-effective, safe, and selective to the pulmonary vasculature; no such agent currently exists. Inhaled nitric oxide selectively reduces pulmonary pressures without systemic hypotension. However, it is expensive, potentially toxic, and requires complex technology for monitoring and administration. Inhaled epoprostenol may be an alternative therapy to minimize systemic hypotension, which often accompanies rapid intravenous titration. To evaluate the safety and efficacy of inhaled epoprostenol in critically ill patients with PAH, we conducted a literature search by using the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases (1966-August 2009) for relevant studies. Case reports and in vitro studies were excluded. Overall, 11 studies met the inclusion criteria. The PAH population included patients requiring cardiac surgery, lung or heart transplantation, or nonspecific intensive care. All trials showed that inhaled epoprostenol significantly decreased pulmonary pressures without lowering systemic blood pressure. The duration of therapy in most studies was 10-15 minutes, with one study evaluating its effects up to an average of 45.6 hours. Pulmonary pressures returned to baseline soon after drug discontinuation. Minimal adverse events were reported. Thus, inhaled epoprostenol in various subgroups of critically ill patients was effective in reducing pulmonary pressures. However, the significance of these effects on improving clinical outcomes remains unknown. Further studies are needed to determine the role of inhaled epoprostenol in critically ill patients with PAH.