The river flow regime is a defining feature of waterways, shaping physical, chemical, ecological, and evolutionary processes. While temporal variation in river flows is generally considered an essential component of river health, the frequency and context of variation can produce different outcomes, especially in the presence of streamflow modification. For example, high frequency flow signatures, caused by diel hydropeaking fluctuations, can stress river health via rapid inundation and desiccation of the varial zone, imposing limits on recruitment for riparian plants and aquatic insects with complex life cycles. Flat signatures arising from flow homogenization produce a static varial zone prone to encroachment of rooted macrophytes and filamentous algae, which are of lower nutritional quality than diatom-based biofilms, and also increase the probability of toxic cyanobacterial blooms. Infrequent but large magnitude high flows can have positive effects on sediment dynamics and stimulate population growth but can sometimes favor invasive species. Here, we examine river frequency spectra across temporal scales and document river health outcomes in terms of physical, ecological, and evolutionary processes. Physical processes include hydrology, hydraulics, temperature regimes, and sediment flux. Ecological processes include population dynamics, biological invasions, species interactions, and cross-ecosystem linkages. Evolutionary processes include population genetics, trait evolution, and phylogenetic structure. We illustrate our findings with examples from rivers where management has altered river frequencies: the Colorado River below Glen Canyon dam (lowered diel flow frequencies that stimulated aquatic insect productivity) and the Klamath River basin (dam removal that altered sediment flux and macrophyte dynamics). We also examine the value of “breaking the brick” – implementing hydrographs that incorporate flow fluctuations with variable frequencies, amplitudes, and phases, rather than imposing seasonally-prescriptive flows or minimum flows that abruptly shift in response to management demands.