The lower reaches of the expansive Murray–Darling Basin, Australia, are a hotspot for freshwater biodiversity. The regional ecosystem, however, has been significantly altered by river regulation, including local and catchment-wide water abstraction. Freshwater fishes have suffered from the resultant altered flow regime, together with other threats including habitat degradation and alien species. Impacts reached a critical point (imminent species extinction) during a prolonged drought (1997–2010) that lead to broad-scale habitat loss and drying of refuges during 2007–2010, and urgent conservation measures were subsequently instigated for five threatened small-bodied fish species. A critical response phase included ad hoc interventions that were later incorporated within a broader, coordinated multi-agency program (i.e. the Drought Action Plan and Critical Fish Habitat projects). On-ground actions included local translocation, alien species control, in situ habitat maintenance (e.g. earthworks, environmental water delivery), fish rescues, artificial refuge establishment and captive breeding. Improved river flows signalled an initial phase of recovery in 2011–2012 that included reintroductions. The present paper aims to document the actions undertaken in the Lower Murray, and review successes and lessons from practical examples that will help guide and inform management responses to conserve fish in modified systems subjected to severe water decline.