The Knights Hospitaller, by now also referred to as the Knights of Rhodes, have been the scourge of Muslim shipping on the eastern Mediterranean for more than two centuries.

The Knights have been forced to become a more militarized order, fighting especially with the Barbary pirates.

They had withstood two invasions in the fifteenth century, one by the Sultan of Egypt in 1444 and another by the Ottoman Sultan Mehmed II in 1480 who, after capturing Constantinople and defeating the Byzantine Empire in 1453, had made the Knights a priority target.

In 1494 they created a stronghold on the peninsula of Halicarnassus (presently Bodrum), using pieces of the partially destroyed Mausoleum, one of the Seven Wonders of the Ancient World, to strengthen their rampart, the Petronium.

An entirely new sort of force arrives in 1522: four hundred ships under the command of Ottoman Sultan Suleiman the Magnificent, who is concentrating his efforts on military campaigns, deliver one hundred thousand men to the island (two hundred thousand in other sources).

Against this force the Knights, under Grand Master Philippe Villiers de L'Isle-Adam, have about seven thousand men-at-arms and their fortifications.

The siege lasts six months, at the end of which the surviving defeated Hospitallers are allowed to withdraw to Sicily.

The defeated Knights of Rhodes sail out of Rhodes on January 1, 1523, with as many of the citizens as choose to follow them, ending two centuries of defiance of the Turks.

Despite the defeat, both Christians and Muslims seem to have regarded the conduct of Villiers de L'Isle-Adam as extremely valiant, and the Grand Master is proclaimed a Defender of the Faith by Pope Adrian VI.