Paradoxical embolism is one of the predominant causes of cryptogenic stroke and interventional secondary prevention, i.e., closure of the patent foramen ovale (PFO), is a much discussed issue. This review aims to provide a complex perspective on this topic, aggregates and comments on the available data and current guidelines. Several large trials were performed, some of which proved the superiority of PFO closure over pharmacotherapy while others have not. Studies detecting significant superiority of intervention worked with disproportionately high representation of large shunts compared to the general population. Other controversies also remain, such as the lack of comparison of the effect of modern anticoagulant/antiplatelet treatment to PFO closure or the risk of developing unwanted side effects after intervention, and these are discussed in detail. PFO closure is a suitable method for secondary prevention of paradoxical embolism and, therefore, cryptogenic stroke. However, this is only true for carefully selected patient populations and such selection is of the utmost importance in deciding on interventional or conservative treatment.