Managing and conserving threatened migratory salmonid populations in large river–lake ecosystems is challenging not only because of the ecosystems’ large size, but also because there is often more than one anthropomorphic stressor. The River Klarälven – Lake Vänern ecosystem, situated in Norway and Sweden, is a large, highly modified ecosystem, home to a threatened, endemic, large-bodied population of landlocked Atlantic salmon (Salmo salar). With 11 dams, the salmon population has been maintained through extensive stocking and a truck and transport system for spawners. Here we review what we have learned about the salmon after 15 years of research, highlighting the major findings for each life stage. Our studies indicate that the salmon population is below carrying capacity, and we suggest measures to increase the number of spawners and downstream passage success. Habitat restoration to compensate for losses from former log-driving activities is expected to further increase carrying capacity. Re-establishing salmon in Klarälven’s upper reaches in Norway, while possible, is fraught with both ecological and legislative hurdles. Substantial long-term funding is needed to foster co-management and ensure a sustainable fishery.