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The island was populated by ethnic groups from the surrounding nations, including Jews. Under Ottoman rule, they generally did fairly well, but discrimination and bigotry occasionally arose. In February 1840, the Jews of Rhodes were falsely accused of ritually murdering a Christian boy. This became known as the Rhodes blood libel.

In 1912, Italy seized Rhodes from the Turks during the Italo-Turkish War. The island's population thus bypassed many of the events associated with the "exchange of the minorities" between Greece and Turkey. Due to the Treaty of Lausanne, the island, together with the rest of the Dodecanese, was officially assigned to Italy. It became the core of their possession of the Isole Italiane dell'Egeo.

Following the Italian Armistice of 8 September 1943, the British attempted to get the Italian garrison on Rhodes to change sides. This was anticipated by the German Army, which succeeded in occupying the island. In great measure, the German occupation caused the British failure in the subsequent Dodecanese Campaign.

On 19 July 1944, the Gestapo rounded up the island's nearly 2,000 Jewish inhabitants to send them to extermination camps. About 160 of the island's more than 600 Greek Jews survived. The Turkish Consul Selahattin Ülkümen succeeded, at considerable risk to himself and his family, in saving 42 Jewish families, about 200 persons in total, who had Turkish citizenship or were members of Turkish citizens' families.

In 1947, together with the other islands of the Dodecanese, Rhodes was united with Greece.

In 1949, Rhodes was the venue for negotiations between Israel and Egypt, Jordan, Lebanon, and Syria, concluding with the 1949 Armistice Agreements.