The role of a patent foramen ovale (PFO) in stroke is still regarded as controversial, as is the optimal strategy of secondary prevention for such patients. The best available evidence is derived from case-control studies, which in all show a statistically significant relationship but cannot be judged as conclusive for methodologic reasons. Besides paradoxic embolism, different pathomechanisms of stroke due to abnormalities of the atrial septum are possible that can rarely be verified in clinical routine. While the risk of stroke recurrence seems to be low at least for younger patients, to date no definite recommendations for secondary prevention can be given. Several ongoing randomized clinical trials might increase the store of evidence in this topic over the next years. However, primary and secondary risk seem to be substantially increased for the combined defect of PFO and atrial septum aneurysm. To allow further risk stratification, other potentially important factors such as shunt size and coagulation disorders should be targeted in future studies.