The large lakes of Sweden, Mälaren, Hjälmaren, Vättern and Vänern, have been subjected to water-quality monitoring for almost four decades. Physicochemical variables, plankton and benthic invertebrates have been regularly assessed. Hydrological and sediment conditions, macrophytes, fish, primary production, bacteria and attached algae have been periodically investigated. The human impact, including industrial activities, was reflected in excessive amounts of organic matter, nutrients, metals and persistent organic compounds. From the late 1960s all municipal sewage works in the catchments of the lakes were upgraded to the highest technical standard, including chemical precipitation of phosphorus, and phosphorus discharge from the sewage works was thereby reduced by 90–95%. In addition, industries were obliged to restrict discharge of harmful substances. The reactions of the lakes to the remedial measures are discussed as well as the value of various indicators. The studies were instrumental in designing a national lake monitoring program. Additionally, results from large lake monitoring have contributed to the establishment of national water-quality criteria including, physical, chemical, and biological indicators.