We suggest that fluvial ecosystems are legitimate users of water and that there are basic ecological principles guiding the maintenance of long-term ecological vitality. This article articulates some fundamental relationships between physical and ecological processes, presents basic principles for maintaining the vitality of fluvial ecosystems, identifies several major scientific challenges and opportunities for effective implementation of the basic ecological principles, and acts as an introduction to three specific articles to follow on biodiversity, biogeochemistry, and riparian communities. All the objectives, by necessity, link climate, land, and fresh water. The basic principles proposed are: (1) the natural flow regime shapes the evolution of aquatic biota and ecological processes, (2) every river has a characteristic flow regime and an associated biotic community, and (3) aquatic ecosystems are topographically unique in occupying the lowest position in the landscape, thereby integrating catchment-scale processes. Scientific challenges for the immediate future relate to quantifying cumulative effects, linking multidisciplinary knowledge and models, and formulating effective monitoring and assessment procedures. Additionally, forecasting the ecological consequences of changing water regimes is a fundamental challenge for science, especially as environmental issues related to fresh waters escalate in the next two to three decades.