The Murray-Darling Basin (MDB) is Australia's food bowl, contributing 40% of agricultural production and supporting a population of over 4 million people. Historically, the MDB supported a unique native fish community with significant cultural, subsistence, recreational, commercial and ecological values. Approximately one-quarter of the MDB's native species are endemic. Changes to river flows and habitats have led to a >90% decline in native fish populations over the past 150 years, with almost half the species now of conservation concern. Commercial fisheries have collapsed, and important traditional cultural practices of First Nations People have been weakened. The past 20 years have seen significant advances in the scientific understanding of native fish ecology, the effects of human-related activities and the recovery measures needed. The science is well established, and some robust restoration-enabling policies have been initiated to underpin actions. What is now required is the political vision and commitment to support investment to drive long-term recovery. We present a summary of 30 priority activities urgently needed to restore MDB native fishes.