Transboundary river-basin management is a challenging task emerging from lack of on-site expert knowledge, high administrative and socioeconomic complexity, various stakeholder interests, and difficulties enforcing international and national law. Therefore, an efficient ‘science–policy interface’ is a crucial ingredient for the successful development and implementation of adequate management strategies. The Danube River Basin (DRB) drains areas of 19 countries with different cultural, political, and environmental legacies. The European Water Framework Directive (WFD) has provided the guiding legal instrument for DRB management since 2000, supported by several multilateral agreements. The International Commission for the Protection of the Danube River (ICPDR) is responsible for the implementation of the WFD in the DRB. It stimulates management-oriented research and coordinates the various activities of the contracting parties and observers, including those of many NGOs and stakeholders. The development of the first DRB Management Plan in 2009 constituted a milestone of cooperation among scientific, political, and public organisations. Key stressors and pressures have been identified, a new basin-wide monitoring network has been established, and numerous conservation and restoration sites have been designated. A major challenge in DRB management will be to establish synergies among the competing interests of navigation, hydropower production, flood protection and nature conservation. This paper examines the strengths and weaknesses of DRB science–policy interactions and outlines future strategies for sustainable development of the DRB as a template for transboundary river basin management.