Abstract Chemical pollution of surface waters is a societal concern around the globe. Key problems in current water quality protection, assessment and management are the narrow focus on a small fraction of the chemicals in commerce, concerns for increasingly diverse chemical emissions, and lack of effective diagnosis and management approaches. In reply, three key concepts to address these challenges were developed and tested. The approaches were developed in the context of the European Union Water Framework Directive, based on principles such as the DPSIR-causal framework (Drivers, Pressure, Status, Impact and Response) and the basic feature that water protection and management should be based on a water-system level approach. Collaborative actions of researchers and stakeholders resulted in: (1) an operationalization and implementation of the solution-focused risk assessment paradigm as proposed in 2009, to improve the utility of risk assessments, (2) the provision of a large set of tools and services to prevent, monitor, assess and manage complex mixture pollution problems, and (3) a strategy and a database on intervention options. These three elements were recognized as core elements to help protecting and improving water quality. Although the methods were developed in the context of water quality problems in Europe, the three elements can be applied globally in water quality protection and management.