An Internationally funded Programme, involving the European Commission, the Global Environment Facility managed by UN Development Programme, the World Bank and the European Bank for Reconstruction and Development, is addressing river basin problems in a unique situation. The solution of these should lead to the prevention of pollution and better water quality, protected ecosystems, sustainable water resources and more efficient sewerage and waste water treatment facilities for the 90 million population living in the region and the reduction of pollution impact on the Black Sea into which the Danube River flows. The paper introduces current Programme activities, the challenges being met and progress. Work is described for implementing a monitoring strategy, an accident emergency warning system and implementation of the 1994 Strategic Action Plan. The applied research activity is explained. The Programme is a major activity with many elements addressing a wide range of environmental problems in the catchment of a major international waterway.