Freshwater biodiversity conservation has received substantial attention in the scientific literature and is finally being recognized in policy frameworks such as the Global Biodiversity Framework and its associated targets for 2030. This is important progress. Nonetheless, freshwater species continue to be confronted with high levels of imperilment and widespread ecosystem degradation. An Emergency Recovery Plan (ERP) proposed in 2020 comprises six measures intended to “bend the curve” of freshwater biodiversity loss, if they are widely adopted and adequately supported. We review evidence suggesting that the combined intensity of persistent and emerging threats to freshwater biodiversity has become so serious that current and projected efforts to preserve, protect and restore inland-water ecosystems may be insufficient to avert substantial biodiversity losses in the coming decades. In particular, climate change, with its complex and harmful impacts, will frustrate attempts to prevent biodiversity losses from freshwater ecosystems already affected by multiple threats. Interactions among these threats will limit recovery of populations and exacerbate declines resulting in local or even global extinctions, especially among low-viability populations in degraded or fragmented ecosystems. In addition to impediments represented by climate change, we identify several other areas where the absolute scarcity of fresh water, inadequate scientific information or predictive capacity, and a widespread failure to mitigate anthropogenic stressors, are liable to set limits on the recovery of freshwater biodiversity. Implementation of the ERP rapidly and at scale through many widely dispersed local actions focused on regions of high freshwater biodiversity and intense threat, together with an intensification of ex-situ conservation efforts, will be necessary to preserve native freshwater biodiversity during an increasingly uncertain climatic future in which poorly understood, emergent and interacting threats have become more influential. But implementation of the ERP must be accompanied by measures that will improve water, energy and food security for humans – without further compromising the condition of freshwater ecosystems. Unfortunately, the inadequate political implementation of policies to arrest widely recognized environmental challenges such as climate change do not inspire confidence about the possible success of the ERP. In many parts of the world, the Anthropocene future seems certain to include extended periods with an absolute scarcity of uncontaminated surface runoff that will inevitably be appropriated by humans. Unless there is a step-change in societal awareness of – and commitment to – the conservation of freshwater biodiversity, together with necessary actions to arrest climate change, implementation of established methods for protecting freshwater biodiversity may not bend the curve enough to prevent continued ecosystem degradation and species loss.