For over two centuries (1532-1737), the Medici, as Dukes of Florence and Grand Dukes of Tuscany, ruled over a western Mediterranean state, which had a mainly European geopolitical sphere of influence. However, the transformation of the House of Medici, from republican primi interpares of Quattrocento Florence to dynastic rulers, occurred at the same moment when the Ottoman Empire rose to the rank of early modern superpower, polarizing Mediterranean politics. The Italian Peninsula became the arena where the cultural forces of the eastern and western Mediterranean converged. As a result, from the early days of their rule, the Medici Grand Dukes became enmeshed in a power dynamic which encompassed war, religion, diplomacy, and economic interests. This collection of essays addresses these very themes and sheds new light on key aspects of the complex relationships between the Medici Grand Dukes and the Levant.