Environmental conditions across whole landscapes impact instream habitats and biological communities. However, these linkages are often not well understood and have not been synthesized for European running waters. Investigators now recognize that human pressures and land-use patterns are a threat to function and ecological integrity of aquatic ecosystems, as they are impacting habitats, water quality, and the biota through complex pathways and on different spatial scales. This dissertation builds on the understanding of how human pressures affect running waters using fish assemblages as indicators. Based on a large European dataset, various human pressures as hydrological, morphological, water quality and connectivity pressures and their combinations were investigated, to find patterns and relationships across Europe. Moreover, pressures were compared with a large number of fish assemblage metrics to show the response of the fish fauna to pressures. In addition, the effect of land use composition on fish assemblages was investigated at the Austrian scale. The results show that the degradation of European rivers is widespread. Water quality degradation as a single pressure is not very common, but many sites are affected by hydromorphological pressures or a combination of pressures (water quality pressures interacting with hydromorphological pressures). Moreover, the analysed fish metrics responded specifically to water quality pressures and hydromorphological pressures in three river types and to multiple pressures in all river types. The fact that many metrics reacted exclusively within one river type supports the hypothesis of a type-specific approach. The current findings help to uncover processes and effects of human pressures on fish assemblages on the European scale. Moreover, they contribute to the further development of cause-effect pathways for selected river types, which is especially important for European river management and restoration.