The patent foramen ovale (PFO) has been increasingly implicated in the aetiology of stroke, particularly in young patients with no other identifiable cause (cryptogenic stroke). The mechanism is by the passage of venous clots through the patent foramen into the arterial circulation, enabling cerebral embolism. Such patients with cryptogenic stroke and PFO are often treated with life-long anticoagulants or antiplatelet agents in an attempt to decrease the risk of a recurrence. Less commonly, surgical closure of the PFO has been undertaken in these patients. However, the recent evolution of closure devices that are delivered percutaneously by standard cardiac catheter techniques now offer an alternative non-surgical option. These alternative therapies are yet to be compared adequately. Two issues remain to be resolved. First, in determining appropriate therapy, patients with cryptogenic stroke may be divided into three groups: those with no PFO but an alternative unrecognized aetiology, those with an 'innocent' PFO and an alternative unrecognized aetiology and those with a causative PFO. The distinction between these groups clearly has important treatment implications. Second, the risk versus benefit of each available treatment modality must be determined for these different patient subgroups. These two issues require resolution before rational evidence-based treatment can be prescribed for patients with PFO and cryptogenic stroke.