The interatrial septum (IAS), a fibromuscular structure separating the right (RA) and left (LA) atrium, plays an important role in both intra- and interatrial conduction. Electropathological changes in the IAS such as discordant activation of theright and left septal layer and conduction disorders may facilitate intraseptal re-entry and promote development of atrial tachyarrhythmias such as atrial fibrillation (AF). Various experimental studies have emphasized the importance ofthe IAS in AF initiation and perpetuation. Moreover, a thicker IAS has been associated with atrial tachyarrhythmias anda lower success rate of catheter ablation. Therefore, it is assumed that the septal interatrial connections, which may be more pronounced in patients with a thicker IAS, may furnish an anatomic pathway for re-entry and may explain failureof catheter ablation therapy. However, the exact role of the IAS in the treatment of AF still remains an enigma. Moreprofound understanding of the role of the IAS in the pathophysiology of AF and other atrial tachyarrhythmias isnecessary to improve success of current therapeutic options and develop new treatment modalities. This review outlines the current knowledge on the relationship between anatomic and electrophysiological properties of theIASanddiscusses its involvement in atrial tachyarrhythmias.