Border regions are commonly perceived as disadvantaged areas marked by peripheral location. Most of them are indeed suffering from the distance to political decision centers and economic core regions. The main reason for this drawback can be found in barrier effects caused by the presence of state borders, leading to a truncation of potential catchment areas. This paper attempts to bring together two different approaches: a spatially oriented approach focusing on cross-border flows and a sociological survey on the perceptions of the border region’s inhabitants. Based on a research project on quality of life and on cross-border interrelations in the southern part of the German–Polish border region, the paper provides a first set of data in order to verify whether cross-border flows increase during the process of gradual opening of state borders. It gives an overview of cross-border interrelations in the fields of demography, employment, economy, education, and tourism. Moreover, it includes the inhabitants’ perception of border effects and their motivations for border crossings, differentiating between the response patterns of German and Polish interviewees. The paper closes with policy options for regional development policy in the investigated border region.