In 1565 the Knights, led by Grand Master Jean de la Vallette (after whom the capital of Malta, Valletta, was named), defended the island for more than three months during the Great Siege by the Turks. The Order remained without a territory of its own until 1530, when Grand Master Philippe de Villiers de l'Isle Adam took possession of the island of Malta, granted to the Order by Emperor Charles V with the approval of Pope Clement VII.

In 1523, after six months of siege and fierce combat against the fleet and army of Sultan Suleiman the Magnificent, the Knights were forced to surrender and abandon Rhodes. Early on the habit of the order was red with a white cross, changed later on to the more well-known black cloak and white cross, which by the thirteenth century had assumed the eight-pointed form familiar today as the Maltese Cross. All the Knights were religious, bound by the three monastic vows of poverty, chastity and obedience. By virtue of the Papal Bull, the Hospital became an Order exempt from all Church authority except for the pope's, and paid no tithes.

With the Bull of 15 February 1113, Pope Paschal II approved the foundation of the Hospital and placed it under the ægis of the Holy See, granting it the right to freely elect its superiors without interference from other secular or religious authorities. John of Jerusalem - the monastic community that ran the hospital for the pilgrims in the Holy Land - became independent under the guidance of its founder, Blessed Gérard. Merchants from the ancient Marine Republic of Amalfi obtained from the Caliph of Egypt the authorization to build a church, convent, and hospital in Jerusalem to care for pilgrims. The birth of the Order dates back to around 1048. John, the Knights of Rhodes, the Knights of Malta, and about a dozen variations thereon, is a Roman Catholic religious order and the oldest and perhaps most important of the three great orders of crusading knights, the other two being The Knights Templar and The Teutonic Knights. The Sovereign Military Hospitaller Order of Saint John of Jerusalem of Rhodes and of Malta (SMOM), known also as The Knights Hospitallers, the Knights of St.

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