The Lambro-Seveso-Olona (L-S-O) system derives from the human regulation of the natural hydrology of the territory around Milan city area. The average population density in the L-S-O area is among the highest in Italy and Europe. Industry is also highly developed in this basin: chemical, textile, paper, pulp and food industries being the most important ones. Although, at present, the L-S-O system no longer receives the untreated wastewaters of the Milan urban area, treated wastewaters constitute about half of the streamflow. Biotic communities in this river have a long history of poor quality status, having suffered great damage due to domestic and industrial discharges. Recently, new chemical quality standards for macropollutants have been set by the Italian legislation as support for the good ecological status according to the Water Framework Directive (WFD). This new index is very restrictive, and it makes it extremely challenging to achieve the water quality objectives for the L-S-O system. The aim of this study is to analyse through a modelling exercise the restoration possibilities of the L-S-O system, investigating both the source apportionment of the macropollutants, the discharge limits that should be set to achieve the good quality status and their corresponding cost.