Observational data from prospective and retrospective trials indicate that a patent foramen ovale (PFO) is associated with the risk of ischemic stroke. The mechanism involved is presumed to be paradoxical embolism from a venous thrombus that travels via the PFO to the systemic circulation causing an ischemic stroke. Primary stroke prevention data for patients with a PFO are nonexistent. Given the substantial prevalence of PFO in the total population (~ 25% to 30%), a primary prevention study may not be feasible. However, whether targeted primary prevention for patients with PFOs of certain morphologic characteristics (eg, larger size, greater degree of shunt) would be possible remains undefined. Given the large number of asymptomatic subjects, no therapy is currently recommended. The best treatment modality to prevent recurrent stroke in patients with PFO has not been defined. There are four major treatment choices: surgical closure, percutaneous device closure, medical therapy with anticoagulants, and medical therapy with antiplatelet agents. Regarding medical therapy, the Patent Foramen Ovale in Cryptogenic Stroke Study has demonstrated that antiplatelet and anticoagulant therapies are of equal benefit in preventing recurrent adverse events. Although closure of the PFO, either surgical or percutaneous, may further reduce the event rates, this remains to be demonstrated because no randomized trial to date has compared PFO closure with medical therapy.