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Rehabilitation of large Anthropocene rivers requires engagement of diverse stakeholders across a broad range of sociopolitical boundaries. Competing objectives often constrain options for ecological restoration of large rivers whereas fewer competing objectives may exist in a subset of tributaries. Further, tributaries contribute toward building a “portfolio” of river ecosystem assets through physical and biological processes that may present opportunities to enhance the resilience of large river fishes. Our goal is to review roles of tributaries in enhancing mainstem large river fish populations. We present case histories from two greatly altered and distinct large-river tributary systems that highlight how tributaries contribute four portfolio assets to support large-river fish populations: 1) habitat diversity, 2) connectivity, 3) ecological asynchrony, and 4) density-dependent processes. Finally, we identify future research directions to advance our understanding of tributary roles and inform conservation actions. In the Missouri River United States, we focus on conservation efforts for the state endangered lake sturgeon, which inhabits large rivers and tributaries in the Midwest and Eastern United States. In the Colorado River, Grand Canyon United States, we focus on conservation efforts for recovery of the federally threatened humpback chub. In the Missouri River, habitat diversity focused on physical habitats such as substrate for reproduction, and deep-water habitats for refuge, whereas augmenting habitat diversity for Colorado River fishes focused on managing populations in tributaries with minimally impaired thermal and flow regimes. Connectivity enhancements in the Missouri River focused on increasing habitat accessibility that may require removal of physical structures like low-head dams; whereas in the Colorado River, the lack of connectivity may benefit native fishes as the disconnection provides refuge from non-native fish predation. Hydrologic variability among tributaries was present in both systems, likely underscoring ecological asynchrony. These case studies also described density dependent processes that could influence success of restoration actions. Although actions to restore populations varied by river system, these examples show that these four portfolio assets can help guide restoration activities across a diverse range of mainstem rivers and their tributaries. Using these assets as a guide, we suggest these can be transferable to other large river-tributary systems.