A patent foramen ovale (PFO) is a common anatomic finding in 20% of the normal population. Significant hypoxemia can occur in circumstances in which hemodynamic or anatomic changes predispose to increased right-to-left intra-atrial shunting. The subsequent hypoxemia produces substantial dyspnea that may affect the patient's quality of life, independent of underlying pulmonary disease. Profound hypoxemia caused by right-to-left shunt across the interatrial septum usually responds to percutaneous PFO closure. An important impediment to successful treatment is the lack of awareness of the potential role of a PFO in this condition.