Patent foramen ovale (PFO) is a remnant of the foetal circulation, found in about a quarter of the population. PFO is an asymptomatic condition and the high prevalence infers that it is in most cases of no or only limited clinical significance. However, recent research has found an increased prevalence of PFO in cryptogenic stroke, decompression illness and migraine. The presence of a PFO has also been associated with oxygen desaturation in conditions such as obstructive pulmonary disease and obstructive sleep apnoea. The rapid evolution and widespread availability of catheter-based closing techniques have further stimulated interest. The seemingly growing significance of PFO will be discussed in this review.