Platypnea-orthodeoxia syndrome is an uncommon condition of positional dyspnea and hypoxemia; symptoms occur when the patient is upright and resolve with recumbency. Causes can be broadly categorized into 4 groups: intracardiac shunting, pulmonary shunting, ventilation-perfusion mismatch, or a combination of these. This video provides an overview of the platypnea-orthodeoxia syndrome.