The platypnea orthodeoxia syndrome (POS) is a rare condition characterized by dyspnea and hypoxia in upright position. Pathopysiologic underlying mechanisms are determined by an atrial right-to-left shunt. Coexisting conditions that evolve POS can be of anatomical nature causing interatrial communication or of functional nature producing a deformity of the atrial septum in upright position. Diagnosis is difficult, as it needs to mention about POS. Classically, transthoracic and transesophageal echocardiography in supine and upright position with use of contrast medium and/or Doppler will point the diagnosis. Treatment is predominantly carried out by interventional closure of atrial septal defect that promptly resolves clinical symptoms.