A Patent Foramen Ovale (PFO) is detectable in 20–25% of the population. Some, but not all, case control studies have found an increased incidence of PFO in patients with cryptogenic stroke. Prospective cohort studies have failed to convincingly demonstrate a link between PFO and first stroke, and evidence linking PFO to recurrent stroke is far from compelling. The rate of recurrent stroke in medically treated patients is low, but the development of devices for PFO closure has lead to enthusiasm in some quarters to pursue a strategy of device closure. Nonrandomized studies have suggested a lower risk of recurrent events with device closure but the data are heterogeneous, and potentially prone to bias. Device implantation is associated with a risk of major adverse events of between 1.5% and 2.3%, and there is a significant rate of failure to close shunts. The results of randomized trials of device closure are keenly awaited. Migraine with aura has been linked with PFO. A recent metanalysis suggested an association, but the one prospective population study did not. The well-publicized and controversial MIST Trial is the only randomized trial of device closure in migraineurs yet published, and failed to demonstrate a convincing benefit from device closure. Other conditions such as platypnea-orthodeoxia syndrome and prevention of decompression sickness in divers, may justify device closure. Evidence for a role of PFO in the etiology of cryptogenic stroke and migraine is contradictory. It is possible that some patients might benefit from PFO closure but there is scant evidence of sufficient quality to justify routine PFO closure in either group. It is essential that ongoing randomized trials of device closure are completed.