The foramen ovale, a remnant from the fetal circulation, remains patent through adulthood in approximately 1/4th of the general population, thus representing the most common persistent abnormality of fetal origin. In these individuals, the patent foramen ovale (PFO) permits interatrial right-to-left shunting during those periods of time when right atrial exceeds left atrial pressure. Recently, the pathophysiological aspects of the PFO have been increasingly appreciated, giving rise to disease manifestations such as paradoxical embolism, refractory hypoxemia in patients with right ventricular infarction or severe pulmonary disease, orthostatic desaturation in the setting of the rare platypnea-orthodeoxia syndrome, neurological decompression illness in divers, and migraine headache with aura. Despite the growing recognition of the PFO, particularly when associated with an atrial septal aneurysm, as risk factor for paradoxical embolism, the optimal treatment strategy for symptomatic patients remains undefined. Most patients with presumed paradoxical embolism are currently treated medically with antithrombotic medications, with a paucity of data concerning the efficacy of oral anticoagulant as opposed to antiplatelet therapy. Surgical PFO closure has proved feasible, but the procedure is associated with the well known complications of cardiac surgery, and the results have been mixed with respect to stroke prevention. The recent introduction of interatrial septal occlusion devices set the stage for a minimally invasive, percutaneous approach. The present article discusses the pathophysiology of the PFO, and the advantages and drawbacks of the different therapeutic options available for symptomatic patients.