The Water Framework Directive (WFD) aims at achieving good ecological status (GES) for surface water bodies throughout Europe, by 2015. Consequently European countries are currently developing and intercalibrating methods based on biological, hydromorphological and physico-chemical quality elements for the assessment of their transitional waters, including fishes. The present work focuses on the response of fish indicators and indices to anthropogenic pressures and natural factors. For doing that, datasets from the Basque and Portuguese estuaries, in the North East Atlantic, have been used. Hence, biological data from fish (and in some cases, crustaceans), together with different types of pressure (population, industry, ports, dredging, global pressures, pollution, channeling, etc.) and hydromorphological data (flow, estuary volume, depth, intertidal surface, residence time, etc.) have been analyzed. Together with fish assemblages composition and individual metrics (richness, trophic composition, etc.), two fish indices (Basque AFI and Portuguese EFAI) have been investigated. Additionally, the response of five fish indices (AFI, EFAI, ELFI, TFCI, Z-EBI) were tested on a common dataset, within Portuguese estuaries, to check the time lag in the metrics’ response to different human pressures and the variability in the strength of responses to those pressures. This work also focuses on the sensitivity analysis of two European fish-based indices (French ELFI and British TFCI) to changes in their respective metric scores through their observed dynamic range. Sensitivity analyses were run simulating different scenarios of metric score changes, taking into consideration the relationship between metrics. This allowed the metrics with stronger influence in the index score and the resulting water body classification to be highlighted. Importantly, the identification of the most influential metrics could help to guide management efforts in terms of achieving GES by 2015. In general, the fish metrics and indices tested responded to anthropogenic pressures in the Atlantic estuarine sites, yet at the individual metrics level environmental chemical quality was the main driver for observed differences. Also, some metrics did not respond to pressures as expected, which is most likely related to sampling gear efficiency, namely the low capture efficiency of diadromous species with beam trawl. The cause-effect relationship study emphasized that fish-based indices developed to assess the water quality of estuarine systems did not detect all the pressures with the same sensitivity in terms of strength and time-lag, and gave more importance to some pressures, namely chemical pollution. The fish-based indices developed to assess the water quality of estuarine systems do not allow the individualization of pressure effects, which may constitute a problem to put forward the correct specific measures for management and rehabilitation of estuaries. On the other hand, some indices also do not seem relevant, in a short time, to detect changes of the ecological quality which may constitute a handicap for management or an indication for their restructuring. The sensitivity analysis indicates that a number of estuarine resident taxa, a number of estuarine-dependent marine taxa, a number of benthic invertebrate feeding taxa and a number of piscivorous taxa have the greatest influence on the TFCI classification. For the French index ELFI, the most influential metrics are mainly DT (total density) and DB (density of benthic species), followed by RT (total richness). These results suggest a high sensitivity of the quality indication provided by these indices on richness related aspects of the fish assemblages. Management should therefore prioritize efforts to conserve or restore estuarine attributes underpinning abundance and ecological diversity, for example the diversity of fish habitats, food resources and shelter or the hydrological integration between coastal and transitional waters.