Although debated, patent foramen ovale (PFO) is still a popular field of interest for cardiovascular catheter-based interventions. On the other hand, atrial septal defect (ASD) represents a natural field of application of transcatheter closure. While there is a common agreement about the management of patients with interatrial left-to-right shunts (LRS), the best management of PFO patients is still being discussed. Meanwhile, some recent consensus documents have been produced with the aim to clarify the proper PFO patients’ management, but the perfect strategy has still not been found. In PFO patients, the real challenge for the clinicians, beside secondary prevention of recurrent stroke, is to identify which are the higher risk patients to refer for treatment and the most adequate device to use among the variety of double umbrella devices currently available in the market. Different meta-analysis, registries, and extended follow-up based on previous large randomized trials suggested that interventional therapy is the most effective treatment, at least with some specific devices, but so far only for patients with previous stroke. Moreover, migraine, orthodeoxia, and other conditions should be fully investigated before firm statement on the benefit of transcatheter closure. The main anatomic and functional characteristics of interatrial septum, obtained with the current available diagnostic tools, such as transcranial Doppler (TDC), transthoracic (TTE), and transesophageal echocardiography (TEE), together with a meticulous evaluation of patient’s history and clinical features remain of paramount importance in patients’ selection and preoperative evaluation. In patients presenting ASD, indications to closure are more clearly stated by current guidelines, although dark zones do still exist regards the amount of pulmonary hypertension, the maximum size of the ASDs, and the possibility to treat also different kind of ASD, such as the sinus venosus defects.