Information about the Dodecanese for the period between the conquest of Constantinople by the Crusaders (1204) and the settlement of the Hospitallers (1309) in Rhodes is inadequate. The island was until 1309 a remote province located at the indefinite southeastern borders of the Byzantine state. Many Byzantine governors had alternated with Genoese admirals in the government of the island after the period of rule by the Gavalades (1204-1250), so the connection with the metropolis of Byzantium was loose. The Gavalades governed in Rhodes as independent rulers and had the right to mint their own coins.
In 1306, the Genoese feudal lord of Rhodes Vignolo di Vigniolo agreed with the Knights Hospitallers that the latter would conquer 2/3 of Rhodes, Leros and Kos. The conquest of those islands was completed in the period between 1306 and 1309 with the assistance of Philip the Handsome, king of France, the king of England, the pope, Charles II of Anjou, king of Naples and Sicily, and the Genoeses. Karpathos and Kasos, which belonged to the family of Cornaro, were not included in their dominion neither was Astypalaia, which was under the rule of the family of Querini of the duchy of Naxos.
The Hospitallers had confronted successfully many an efforts of the Ottoman Turks to conquer Rhodes. The second siege (26 June 1522 until 2 January 1523) was marked by the treachery of the chancellor Andre d’Amaral and by the policy of the Ottomans to address to the debilitated Rhodian people with promises as to the respect of their life and religion, in case of surrender, thus outflanking the leaders of the Rhodians. In December 1522 a delegation of Latins and Greeks was forced to declare that they accepted the terms of peace of the Ottoman sultan Suleiman the Magnificent, to whom had surrendered Rhodes and the other castles of the Hospitallers in the Dodecanese.
After the formal signature of the treaty, the Hospitallers together with 4-5 thousands people and the Greek metropolitan abandoned the island on the 1st of January 1523 and departed for Crete. Those islands of the Dodecanese that had not yet been conquered surrendered the one after the other. That is how a period of 213 years of western rule in Rhodes came to an end. The island was once again united - politically as well - with its vital space, Asia Minor. For the mass of the Rhodian people this change meant only change of ruler. After a period of wandering the Hospitallers asked from Charles V of Spain to transfer their seat to Malta, which was ceded to them in 1530, and are known since as the Knights of Malta.