The Murray–Darling Basin (MDB) covers 1.1 million km2, involves six legislative jurisdictions, a myriad of different agencies and illustrates the many complexities of managing fishes, people and water. Its rivers provide water for agriculture, are highly regulated and generally in poor health. Water allocation reform is underway to improve ecological condition but provision of water for environmental outcomes competes with agricultural requirements. Murray–Darling Basin rivers and fishes are important culturally and contribute substantially to tourism and recreational fishing. The MDB has a low number of fish species, now estimated to be at 10% of their pre-European abundance, and all subject to a range of threats, many related to water use and associated infrastructure. The MDB Native Fish Strategy takes a coordinated, long-term, whole-of-fish-community approach to address priority threats and rehabilitate populations. This strategy provides a holistic approach with many actions that complement the potential benefits of water reform.