The currently developing cross-border cooperation among the regions of Eastern Slovakia and Transcarpathia – part of the European Union’s strategy (“Europe 2020”) – can benefit from their common historic and cultural heritage. The general reference is to the impressive histories and the uncommonly complicated destinies of the regions’ individuals and their entire societies. Both phenomena have to be viewed in the geopolitical and historical context of (the often idealized) Middle Europe as a macro-region whose core was formed by the Austro-Hungarian Empire in the 18th and 19th centuries. Eastern Slovakia and Carpathian Ruthenia in their positions as a region (or regions) of the Middle European Habsburg Empire often lagged behind economically and societally compared to the West; they struggled with the religious and ethnic plurality, or more precisely, were intolerant of them. Their dramatic destinies were characterized by an uncertain statehood (unstable statehood coordinates), by their distrust against the political and religious elites; they could not fulfil their role as a barrier against the dangers from the East – Eastern Orthodox Russia and Muslim Ottomans.