Early in 1523, the Hospitallers had to leave Rhodes with a small number of ships, after a long siege by the Ottoman forces under Sultan Soliman I. The Hospitaller rule on Rhodes and the Dodecanese had been endangered at least since the middle of the fifteenth century, but the Order had successfully resisted both the sieges by the Mamluks in the 1440s and by the Ottomans in 1480. The paper discusses the perception of a growing danger for Rhodes after the fall of Belgrade (1521) and the measures taken by the Order, based on the surviving registers from the years 1521/1522. While regular administration continued, the new Grand Master fr. Philippe Villiers de l’Isle-Adam who reached Rhodes in September 1521 had to handle the situation. The appeals to the Emperor, the Kings of England and France, the Pope and others set aside, fr. Villiers focussed on strengthening the fortifications, gathering supplies and monies and revising the Order’s contingent on Rhodes. Internal problems were mostly overcome, but without relief from the Western powers who were at war with each other, the Order finally had to surrender.