The definition of priority substances (PS) according to the Water Framework Directive (WFD) helped to remove many of these chemicals from the market and to reduce their concentrations in the European water bodies. However, it could not prevent that many of these chemicals have been replaced by others with similar risks. Today, monitoring of the PS-based chemical status according to WFD covers only a tiny fraction of toxic risks, extensively ignores mixture effects and lacks incentives and guidance for abatement. Thus, we suggest complement this purely status-related approach with more holistic and solution-oriented monitoring, which at the same time helps to provide links to the ecological status. Major elements include (1) advanced chemical screening techniques supporting mixture risk assessment and unraveling of source-related patterns in complex mixtures, (2) effect-based monitoring for the detection of groups of chemicals with similar effects and the establishment of toxicity fingerprints, (3) effect-directed analysis of drivers of toxicity and (4) to translate chemical and toxicological fingerprints into chemical footprints for prioritization of management measures. The requirement of more holistic and solution-oriented monitoring of chemical contamination is supported by the significant advancement of appropriate monitoring tools within the last years. Non-target screening technology, effect-based monitoring and basic understanding of mixture assessment are available conceptually and in research but also increasingly find their way into practical monitoring. Substantial progress in the development, evaluation and demonstration of these tools, for example, in the SOLUTIONS project enhanced their acceptability. Further advancement, integration and demonstration, extensive data exchange and closure of remaining knowledge gaps are suggested as high priority research needs for the next future to bridge the gap between insufficient ecological status and cost-efficient abatement measures.