River ecosystems are highly biodiverse, influence global biogeochemical cycles, and provide valued services. However, humans are increasingly degrading fluvial ecosystems by altering their streamflows. Effective river restoration requires advancing our mechanistic understanding of how flow regimes affect biota and ecosystem processes. Here, we review emerging advances in hydroecology relevant to this goal. Spatiotemporal variation in flow exerts direct and indirect control on the composition, structure, and dynamics of communities at local to regional scales. Streamflows also influence ecosystem processes, such as nutrient uptake and transformation, organic matter processing, and ecosystem metabolism. We are deepening our understanding of how biological processes, not just static patterns, affect and are affected by stream ecosystem processes. However, research on this nexus of flow-biota-ecosystem processes is at an early stage.We illustrate this frontier with evidence from highly altered regulated rivers and urban streams. We also identify research challenges that should be prioritized to advance process-based river restoration.