Patent foramen ovale (PFO) is experiencing increased clinical interest as a congenital cardiac lesion persisting into adulthood. It is implicated in several serious clinical syndromes, including stroke, myocardial infarction, and systemic embolism. The PFO is now amenable to percutaneous interventional therapies, and multiple novel technologies are either available or under development for lesion closure. The PFO should be better understood to take advantage of emerging percutaneous treatment options. This paper reviews PFO anatomy, pathology, pathophysiology, and clinical impact and discusses current therapeutic options.