Medeion is first mentioned as a place where Spartan troops crossed as part of the Peloponnesian War. Some time later, it probably became a member of the Akarnanian Confederation.
After the death of Alexander the Great, Medeion successfully resisted Aetolian domination for a hundred years. In 231 BCE, obviously not wanting to extend it another hundred years, the Aetolians put the city under siege but were ultimately defeated by an army of Illyrian mercenaries hired by Demetrios II of Macedonia.
The original fortification is still in good condition.
Medeion is crossed by the Spartan army on its march to the Battle of Olpai, where Athens defeated them.
Medeion maintains its independence from the Aetolian League, unlike many of their neighbors.
The Aetolian League besieges Medeion, but are defeated by reinforcements sent by Demetrios II of Macedon.
Antiochos III takes Atrax, by then a Roman stronghold, and Medeion.