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Sustainable management of water resources calls for integration of ideas and approaches and revolves around assessment of causal-effect relationships as tools towards defining informed mitigation options and planning. The current paper presents a new holistic approach developed within the Globaqua Coordination Project that combines indicator-based well-established and tested concepts towards developing informed Programmes of Measures and River basin management plans: a. The DPSIR framework that has been engaged as central instrument to address the Water Framework Directive requirements and the concepts embedded in the Integrated Water Resource Management; b. The Ecosystem Services Approach emphasizing on the links between ecosystem services, changes in ecosystems and human well-being, c. Scenario assessment for valuation of future conditions to ensure the sustainability in the use of water resources. The implementation of the new combined framework in two river basins, Ebro in Spain and Evrotas in Greece, stressed the need for revised options targeting elimination of water pollution, measures to ensure water supply that covers the demand even under conditions of climate change and increased water stress and the need for improved valuation of environmental and resource use costs. (C) 2019 The Authors. Published by Elsevier B.V.