Rivers are fascinating natural systems, underpin ecosystem and societies, and “flow” through many global challenges, from climate adaptation and mitigation to natural hazards, meeting human needs for water, energy, and food, and tackling the global biodiversity crisis. At the same time, rivers are heavily altered by human activities, requiring conceptualizing their functions and management at the intersection of human and natural systems. The Schmitt Lab for River System Science and Sustainability (RS3) focuses on developing new models to understand river processes, from sediment transport to biodiversity and water quality, and leverages those models to solve environmental challenges. Our research highlights, for example, how sediment transport is critical for climate adaptation in the world’s large rivers and how new network models enable strategic planning that reduces the impacts of future dams on sediment. Additional research interests include coupling of catchment and river processes, river management under deep uncertainty, understanding future roles for river infrastructure, and quantifying the multifaceted roles of rivers for societies and human development.