The Expulsion of Heliodorus, from whom the room takes its name, illustrates the biblical episode (2 Maccabees, 3:21-28) of Heliodorus, sent by the king of Syria Seleucus, to take over the treasure preserved in the temple of Jerusalem. At the request of the high priest Onias, God sends a horseman assisted by two youths who beat and banish Heliodorus.

The commissioning pontiff (Julius II) has himself shown as witnessing the scene (in the foreground on the left) seated in the gestatorial chair, carried on the shoulders of the chair bearers. Of these, that on the left is a portrait of Marcantonio Raimondi, engraver and friend of Raphael, who is himself portrayed in the other figure to the right.

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"The choice of this episode is clearly an allusion to the need for Julius II to expel foreigners from Italian territory and internal enemies from the territories of the Church."
-- Enrico Bruschini, 'Vatican Masterpieces'