This work aims to reconstruct the genesis and the evolution of the frontier between Liguria and Provence and its impact on local societies over a wide chronological span. The specific area of research is the Nervia Valley: the only, among the valleys of western Liguria and the region of Nice, to have constituted for more than five centuries (1262-1796) a frontier between two countries often in conflict, the Republic of Genoa in the east and Angevin Provence (later Savoy) in the west. Based on a thousand documents preserved at the archives of three European states (France, Italy and Monaco), the study firstly highlights both the economic and strategic importance of the Nervia Valley in the alpine and Mediterranean contexts; the road network, economic and settlement policies pursued in this area by Genoa, Provence and the House of Savoy; and the complex, and not always smooth, relations between Lords and communities. The second part of the work investigates the local societies in the Sixteenth century, a period of transition between the Middle Ages and the Modern Era. Special attention is devoted to the Doria of Dolceacqua, the only aristocratic family in this valley, and to their role in the industrial development of the territory as wine, olive oil and paper entrepreneurs; to the diffusion of the ideas fostered by the Reformation in the villages governed by the duke of Savoy; and to the post-Tridentine Catholic renewal. The final part tries to assess to what degree the presence of a frontier influenced the life and daily activities of the inhabitants, and if this presence was preponderant or not in comparison to another important factor which determined the character of this valley in the course of time: the passage of trade routes from the Ligurian coast to southern Piedmont.