This paper examines cross-border co-operation (CBC) and associated cross-border regions (CBRs) emerging within the European Union (EU). It analyses both as processes of institution building utilizing recent theories of governance and networks. The discussion is organized in four parts: (1) an overview of CBC in the EU to date and a suggested theoretical framework for understanding it; (2) a specification of CBC governance institutions as an articulation of horizontal and vertical networks; (3) an outline of the interests and agendas of the main actors involved in CBC, including the EU Commission as well as local, regional and central state authorities; and (4) an assessment of CBC governance as the outcome of the aggregate effects of the institutions and actors involved. The concluding section locates CBC within the emerging EU polity, arguing that it represents an example of the building of multi-level governance networks. CBRs, although loosely articulated, are characterized as terrains for producing new transnational actors and new opportunities for existing actors.