The city of Constantinople fell to the Ottoman Turks, an event that deeply impacted Renaissance politics and is indirectly referenced in the game's setting.
The flourishing of culture, arts, and humanism in Italy began, setting the backdrop for much of Assassin's Creed II’s events.
Lorenzo de’ Medici, a major patron of the arts and ruler of Florence, whose period of influence corresponds with the game's timeline.
The Pazzi conspiracy, an attempt to overthrow the Medici family in Florence, including the assassination of Giuliano de’ Medici, took place.