Meeting sustainable food production challenges requires efficient ways to manage nutrients and mitigate the losses of nitrogen (N) and phosphorus (P) to water. Future nutrient management therefore requires a clearer understanding of the relative influence of soils, geology, farm practice, landscape and weather on the propensity for nutrients to be lost to water. Within the Agricultural Catchments Programme (ACP), environmental, agronomic and socioeconomic data have been gathered since 2009, using the same experimental methodology in five meso-scale river catchments, and one karst spring zone, covering a range of soils, landscapes and farming systems. The ACP has contributed to a better understanding of nutrient mobilisation and transfer pathways and highlighted the influence of the physical and chemical environment as well as agricultural and meteorological drivers on diffuse nutrient loss to ground and surface waters. The environmental quality standards were breached for N and/or P in some of the catchments, but for different reasons and not always clearly linked to the source pressures within the catchment. There are clearly no one-size-fits-all solutions for mitigation of nutrient losses to water. A better understanding of the underlying processes is required to identify critical source areas, to select mitigation strategies, when to implement them and to build realistic expectations of their impact. Sustainability in an agricultural setting is not confined to environmental issues, but also includes social, economic and innovative aspects. To maximise farmers’ uptake of environmental measures, the actions should encompass all these aspects of sustainability. Integrated knowledge transfer is key.