The European Union Water Framework Directive represents a new, holistic approach to safeguarding water quality and improving aquatic ecosystems. The challenges faced by managers of multinational river basins are highlighted in the River Danube system, which covers an area exceeding 800,000 km2, incorporating all or part of 14 countries. This study investigates the challenges faced with attempting to achieve and maintain ‘good’ status for water quality due to the widespread occurrence of metal mining activity throughout the Danube drainage basin. The release of contaminant metals (notably Cd, Cu, Pb, Zn) and As from point and diffuse sources results in solute metal loads within certain affected rivers that exceed 3000 kg/day, causing metal concentrations to exceed water quality guidelines by up to 280 times and giving rise to the associated degradation of aquatic environments. Within mining-affected catchments, contaminant metals and As are being dispersed over a variety of spatial scales, with the dispersal of sediment-associated metals occurring over hundreds of kilometres resulting in the mobilization of contaminants across international borders. Establishing efficient contamination management and remediation strategies within the Danube drainage basin will be influenced by predicted increases in winter flood frequency, which will potentially increase the mobilization of contaminants from point and diffuse sources.