The increasing expression of human activity, climate variability, and climate change on humid, terrestrial hydrologic systems has made the integrated nature of large river basins more apparent. However, to date, there is no instrument platform sufficient to characterize river basins' hydrologic couplings and feedbacks, with many processes and impacts left almost entirely unobserved (e.g., snowmelt floods). Characterization at the river basin scale will require a more holistic vision and a far greater commitment from the environmental science community. It will require new designs and implementation of integrated instrumentation, a new generation of models, and a management framework that clearly addresses the human-climate-terrestrial interactions impacting our watersheds and river basins. Initially, we propose that existing “similarity classifications” (e.g., regional soil, geologic, ecologic, hydrographic digital products) can provide a starting point for organizing historical data and initiating a long-term adaptive, multiscale observing strategy. This vision paper outlines instrumentation platforms for point, plot, reach, and hillslope scales that could be located within the “characteristic” landscapes of river basins. The network of observing platforms then forms the basis of a “Hydro-Mesonet” that can potentially support multiscale, multiprocess scientific studies necessary to understand and improve forecasts of our water resources at the river basin scale. This paper concludes with a discussion of how a network of such sites can support research at the level of the individual researcher and scale to the level of community-wide initiatives.