The Siege of Malta (also known as the Great Siege of Malta) takes place in 1565 when the Ottoman Empire invades the island, then held by the Knights Hospitaller (also known as the Sovereign Order of Saint John of Jerusalem of Rhodes and of Malta, Knights of Malta, Knights of Rhodes, and Chevaliers of Malta)The Knights win the siege, one of the bloodiest and most fiercely contested in history, and one which becomes one of the most celebrated events in sixteenth century Europe.

Voltaire said, "Nothing is more well known than the siege of Malta," and it unquestionably puts an end to the European perception of Ottoman invincibility and marks a new phase in Spanish domination of the Mediterranean.

The siege is the climax of an escalating contest between a Christian alliance and the Ottoman Empire for control of the Mediterranean, a contest that includes Turkish corsair Turgut Reis's attack on Malta in 1551, and the Turks' utter destruction of an allied Christian fleet at the Battle of Djerba in 1560.