Water regulation world-wide is moving to a new and challenging paradigm characterised by integrated assessment and management of multiple pollution loadings within drainage basins. This is seen in the European Water Framework Directive and the United States Clean Water Act. Implementation lessons of the latter suggest the principal water quality concern at the continental scale is microbial pollution by faecal indicators and pathogens. This presents a major new challenge to the microbiological community and presents major opportunities of joint working with catchment scientists, modellers, engineers and the farming community. To date, very little catchment-scale science has addressed microbial flux measurement, modelling and prediction when compared to other parameters such as the nutrients, oxygen demand and sediments. The engineering community has made excellent progress on point-source pollution control from sewage works but, parallel progress on agricultural best management practices to limit diffuse-source pollution from agriculture is less evident and the science evidence-base for the efficacy of such measures remains equivocal. This contribution presents a clear set of research challenges and management priorities designed to stimulate further involvement by the microbiological community in this emerging area.