Freshwater fishery plays a critical role in the national economy. With the great achievements having been made in both production and value, its development is severely pressured by the aquatic environmental pollution. Consequently, an innovative approach of “Freshwater Mussel Watch” system was firstly proposed in 2003 using Anodonta woodiana as unique bioindicators for aquatic environments. To date, the approach has been successfully employed to bio-monitor, assess, and early warn various inorganic (especially heavy metals) and organic pollutants in different waters (especially lakes, rivers, and ponds) within China and around the world. Moreover, breakthroughs have been achieved on pollutant toxicology, bioaccumulation kinetics, and water purification by the approach. This paper summarizes the advances to date of “Freshwater Mussel Watch” approach on the studies of passive biomonitoring, active biomonitoring, and the development of model animals for freshwater environments for providing useful references to effectively monitor, assessment and conservation of fisheries and aquatic environment, as well as interpreter the corresponding toxic mechanism.