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The complete division of the atrial cavity by a septum, resulting in a left and right atrium, is found in many amphibians and all amniotes (reptiles, birds, and mammals). Surprisingly, it is only in eutherian, or placental, mammals that full atrial septation necessitates addition from a second septum. The high incidence of incomplete closure of the atrial septum in human, so‐called probe patency, suggests this manner of closure is inefficient. We review the evolution and development of the atrial septum to understand the peculiar means of forming the atrial septum in eutherian mammals. The most primitive atrial septum is found in lungfishes and comprises a myocardial component with a mesenchymal cap on its leading edge, reminiscent to the primary atrial septum of embryonic mammals before closure of the primary foramen. In reptiles, birds, and mammals, the primary foramen is closed by the mesenchymal tissues of …