We illustrate the fundamental importance of fluctuations in natural water flows to the long-term sustainability and productivity of riverine ecosystems and their riparian areas. Natural flows are characterized by temporal and spatial heterogeneity in the magnitude, frequency, duration, timing, rate of change, and predictability of discharge. These characteristics, for a specific river or a collection of rivers within a defined region, shape species life histories over evolutionary (millennial) time scales as well as structure the ecological processes and productivity of aquatic and riparian communities. Extreme events – uncommon floods or droughts – are especially important in that they either reset or alter physical and chemical conditions underpinning the long-term development of biotic communities. We present the theoretical rationale for maintaining flow variability to sustain ecological communities and processes, and illustrate the importance of flow variability in two case studies – one from a semi-arid savanna river in South Africa and the other from a temperate rainforest river in North America. We then discuss the scientific challenges of determining the discharge patterns needed for environmental sustainability in a world where rivers, increasingly harnessed for human uses, are experiencing substantially altered flow characteristics relative to their natural states.