Foramen ovale plays an important function in the fetus but is of no physiologic significance after birth and closes in most individuals. In about one fourth of the population, however, foramen ovale remains open for life and has been associated with cerebrovascular accidents, especially in younger patients, presumably through paradoxical embolism. Patent foramen ovale (PFO) has also been associated with hypoxia, migraine headaches and neurologic findings of decompression illness in scuba divers. Availability of transesophageal echocardiography and its frequent use in the management of patients with stroke has lead to frequent detection of PFO. In addition, the recent development of devices and techniques for percutaneous closure of PFO has resulted in widespread enthusiasm for such interventions, even when a clear etiologic role for PFO may not be established. In the United States, the Federal Drug Administration (FDA) has approved two such devices through compassionate investigational device exemption without adequate data from large randomized clinical studies. Other such devices are undergoing evaluation in clinical trials. Expert opinions have been helpful for clinical decision making in management of patients with PFO associated with stroke, hypoxia, decompression sickness and migraine headaches.