Water allocation among human and natural resource uses in the American West is challenging. Western rivers have been largely managed for hydropower, irrigation, drinking water, and navigation. Today land and water use practices have gained importance, particularly as aging dams are faced with re-licensing requirements and provisions of the Endangered Species and Clean Water Acts. Rising demand for scarce water heightens the need for scientific research to predict consequences of management actions on habitats, human resource use, and fish and wildlife. Climate change, introduction of invasive species, or restoration of fish passage can have large, landscape-scaled consequences - research must expand to encompass the appropriate scale and by applying multiple scientific disciplines to complex ecosystem challenges improve the adaptive management framework for decision-making.