The siege of Rhodes of 1522 was the second and ultimately successful attempt by the Ottoman Empire to expel the Knights of Rhodes from their island stronghold and thereby secure Ottoman control of the Eastern Mediterranean. The first siege in 1480 had been unsuccessful. Despite very strong defenses, the walls were demolished over the course of six months by Turkish artillery and mines.

The siege of Rhodes ended with an Ottoman victory. The conquest of Rhodes was a major step towards Ottoman control over the eastern Mediterranean and greatly eased their maritime communications between Constantinople and Cairo and the Levantine ports. Later, in 1669, from this base Ottoman Turks captured Venetian Crete.