Since initial reports of its association with ischemic stroke appeared in 1988, there has been continued controversy regarding the existence and strength of the association between patent foramen ovale (PFO) and ischemic stroke. Many case-control studies have reported an association between incident cryptogenic ischemic stroke and PFO, yet population-based studies have failed to confirm this association. Studies of the risk of recurrent stroke in patients with cryptogenic stroke with or without PFO have not shown an increased risk of recurrent stroke in patients with PFO. Meanwhile, use of devices to close PFOs and atrial septal defects percutaneously has increased dramatically since their introduction. Completion of the randomized clinical trials of PFO closure currently in progress is vital to determine if the benefits of PFO closure in cryptogenic stroke outweigh its risks.