Portugal and Spain share one of the oldest national borders in the world. It has remained practically unchanged for 800 years. As a result, formal cross-border cooperation processes between the two Iberian countries have only engaged in significant formal partnerships since the 1990s, following the implementation of the EU Interreg-A Community Initiative. Over time, this initiative (later transformed into an EU Cohesion Policy goal – European Territorial Cooperation) contributed to the exponential growth of cross-border cooperation processes, creating more than 100 cross-border entities across the Portuguese–Spanish border. These included not only Euroregions, and later European Groupings of Territorial Cooperation (EGTCs), but also several Eurocities close to the border. Indeed, in the context in which the Portuguese–Spanish border region faces a dramatic depopulation process over vast areas, the role of border cities is particularly relevant to retain population and economic activities in the border area. As such, this chapter analyses border cities and their contribution to the territorial development of the Portuguese–Spanish border region. A more detailed analysis is performed in the case of the Eurocity Elvas (PT)–Badajoz (ES).