A patent foramen ovale (PFO) is a common, incidental echocardiographic finding in otherwise healthy and asymptomatic infants and children. However, a variety of clinical conditions have been ascribed to the presence of a PFO in childhood, such as cryptogenic stroke, platypnea-orthodeoxia syndrome, decompression sickness and migraine, although the data on these are controversial and sometimes contradictory. This review discusses embryology and correlation with post-natal anatomy, anatomical variations of the atrial septum, diagnostic modalities in special circumstances of PFO associated clinical syndromes, and the role of PFO in congenital heart disease, pulmonary hypertension, dilated cardiomyopathy and heart failure in children who require an extracorporeal membrane oxygenator or ventricular assist device as life support.