The physical characteristics of the Guadiana estuary and the richness of its adjacent territories were essential in defining the historical and cultural context of the entire region. The extended navigability of the estuary was fundamental to establish trade routes with the Mediterranean civilizations, namely with the Phoenicians, Greeks, and Carthaginians. These civilizations created several commercial harbors along the Guadiana, namely in Mértola, Alcoutim, Castro Marim and Ayamonte. In these locations the human presence dates back as far as the Neolithic (12,000 to 4,000 BCE) and the Chalcolithic periods (4,000 to 3,100 BCE). Later, the Romans (II BCE to V CE), the Alans (V to VI CE.), the Visigoths (VI to VIII CE), and the Arabs (VIII to XIII CE) successively settled in this Iberian region, until the borders of the continental Portuguese territory were set in the 13th century. The predominant North-South direction of the estuary is intrinsically linked with the definition of the Portuguese and Spanish territories, as it serves as a natural border in its last 50 km. Ore extraction and cereal production in the surrounding areas of the estuary turned Mértola into the most important trading center, up to the Portuguese conquest in 1238 (Fig. 6.1). Copper, iron, and manganese were the main ore resources, but silver and gold were exploited as well. With the Portuguese conquests, the economic importance of the Guadiana estuary decreased sharply. In the 15th and 16th centuries, cereals were shipped to the Portuguese forts of northern Africa, but it was only in the late 19th century that all the regions around the estuary had a new economic burst.