The dynamics of many large floodplain rivers are dominated by the flood pulse. The high kinetic energy of the erosive flows associated with the flood pulse forms and reforms the river channel. In general, the flood pulse supports the immense abundance and diversity of river life by transporting nutrients and organic matter into backwaters in spring, supporting primary and secondary production during the summer and redistributing these products to channels as water levels recede. Both North American and South American fluvial-dependent large river fishes exhibit complex, system-level longitudinal and/or lateral movements across life stages that allow them to exploit flood pulse-driven spatial heterogeneity and seasonal connectivity to feed, reproduce and avoid harsh conditions. We argue that two hydraulic variables, the magnitudes of velocity and the spatial velocity gradient, are necessary and sufficient to both understand fish ‘hydro-navigation’ as well as explain patterns in biogeochemistry and fluvial geomorphology and thereby create a new conceptual framework for large floodplain rivers integrating fluid dynamics, channel morphology, biogeochemical cycling and important elements of fish ecology. We illustrate the framework using summary data from the São Francisco River, Brazil that contains sub-basins possessing different levels of impact and also from the lower Paraná River (Argentina) where natural processes can still be studied. We believe the framework is an important element of large river restoration because it directly links the unique physical and chemical processes of large floodplain rivers to life requirements important to fishes and other biota. Copyright © 2011 John Wiley & Sons, Ltd.