Patent foramen ovale (PFO) is a common developmental anomaly that allows for the passage of blood and other substances from the venous to the arterial circulation. The study of PFO closure has been challenging due to widely available off-label closures performed outside the clinical trial setting. To date, no study has demonstrated benefit of closure using intention-to-treat analyses. Secondary and subpopulation analyses suggest that there is benefit to closure in patients with atrial septal aneurysms and/or substantial degrees of right-to-left shunting. This article reviews the history, associated technologies, and current data regarding PFO closure.