Platypnea-orthodeoxia syndrome (POS) is a rare but clinically important form of dyspnea. The syndrome is characterized by dyspnea and arterial oxygen desaturation that occurs in the upright position and improves with recumbency. In cardiac POS, an atrial septal defect or patent foramen ovale allows communication between the right-and left-sided circulations. A second defect, such as a dilated aorta, prominent eustachian valve, or pneumonectomy, then contributes to right-to-left shunting through the interatrial connection. Diagnosis is made through pulse oximetry to confirm orthodeoxia and through transesophageal echocardiography with bubble study to visualize the shunt. Although data are limited for this rare syndrome, percutaneous closure has thus far proven safe and effective.