The occlusion of a patent foramen ovale (PFO) is one of the most promising and controversial issues of interventional cardiology, with an increasing number of procedures, indications and scientific publications. Although this procedure is considered relatively feasible and efficacious, complications may occur, and the balance between risks and benefits is not always favorable. Data on long-term safety and efficacy are also lacking. From cryptogenic stroke in young patients, indications for occlusion have been extended to include patients with drug-refractory migraine. In this setting, the prevalence of PFO is higher than in the general population, suggesting a possible pathogenetic role. Pathophysiology of this condition and evidence to support occlusion of PFO are incomplete, but a trend towards improving has been reported in many retrospective studies. The only randomized study for migraine benefits in PFO occlusion (MIST) has failed to show a reduction in frequency and intensity of attacks. Selection criteria for patients who will most probably benefit from occlusion are needed. The aim of this brief analysis is to focus the pathophysiological and diagnostic issues on migraine, evaluate their relation with PFO, and review studies to outline percutaneous closure indications.