Aquatic ecosystems facing multiple stressors lead to challenging conditions for their management, as stressors can have additive, but also interactive effects on organisms, populations and communities. Accounting for these interactions is important in the assessment of the stressor’s impacts and to implement good restoration measures. Using a comparable modelling approach and large environmental and fish databases, the combined effect of water quality problems and hydrological stressors were assessed, based on characteristics of fish assemblages observed in rivers, lakes, reservoirs and estuaries of Europe. The effects of nonnative species in interaction with eutrophication and alteration of hydromorphology were also tested for fish assemblages of natural lakes and reservoirs. We show that for all the water body types, water quality problems are a major threat that impacts fish assemblages. Similarly, alteration of the hydro-morphology explains a large part of the composition of river and estuarine fish assemblages. Conversely, we fail to demonstrate an effect of this stressor on the fish community of lakes and reservoirs, as sufficient data are not available yet. However, in these standing waters the introduction of non-native species can explain the variability of some characteristics of fish assemblages. In a second step, we analysed the interactive effect of various stressors. Without interaction, the effect of two stressors on a fish assemblage characteristic corresponds to the sum of the individual effects. This additive effect was compared with the effects really observed in the assemblages to determine the type of interaction. The comparison was done for each fish assemblage characteristic impacted by stressors in each water body type. A large variability of multi-stressor impacts was observed, leading to higher or lower effects than expected in absence of interactions. These results suggest to consider all potential stressors and interactions in the development of fishbased tools dedicated to ecological status assessment or restoration monitoring whatever the water body type is.