Patent foramen ovale (PFO) is associated with a number of clinical syndromes in which it plays variable roles that, often, cannot be accurately determined. This situation creates conflicting data and controversial studies. However, in 2017 and 2018, four randomized clinical trials have been published, allowing for the clarification of certain issues pertaining to cryptogenic stroke. Shortly after this, 8 European scientific societies collaborated to publish the first official international position paper on PFO and cryptogenic stroke, based upon best-available evidence. In the current report, the main positions are presented, relating to PFO diagnosis, general management, and therapeutic choices. Generally speaking, given the complexity of PFO roles, an interdisciplinary and personalized approach was chosen, especially taking into consideration patient involvement at all stages of management. This approach is not suitably addressed by standard guidelines, but can be accommodated in a position statement like this. For this reason, it was possible to offer an approach capable of aiding clinicians to make rational, patient-shared decisions, even when the available evidence is either weak or scarce.