In many world regions the availability of clean water is at risk. Pollution of rivers and coastal seas poses a threat to aquatic ecosystems and society. Here, we review representative examples of mathematical models that simulate pollutant ﬂows from land to sea at global and continental scales. We argue that a multi-pollutant modelling approach would help to better understand and manage water quality issues. Pollutants often have common sources and multiple impacts. Most existing spatially explicit models, however, focus on one type of pollution only. A new generation of models is needed to explicitly address the combined exposure of surface waters to multiple pollutants. Such models could serve as a basis for integrated water quantity and water quality assessments.