It is generally agreed that river rehabilitation most often relies on restoring a more natural flow regime, but credibly defining the desired regime can be problematic. I combined four distinct methods to develop and refine month-by-month and event-based flow recommendations to protect and partially restore the ecological integrity of the Cache la Poudre River through Fort Collins, Colorado. A statistical hydrologic approach was used to summarize the river's natural flow regime and set provisional monthly flow targets at levels that were historically exceeded 75% of the time. These preliminary monthly targets were supplemented using results from three Poudre-specific disciplinary studies. A substrate maintenance flow model was used to better define the high flows needed to flush accumulated sediment from the river's channel and help sustain the riparian zone in this snowmelt-dominated river. A hydraulic/habitat model and a water temperature model were both used to better define the minimum flows necessary to maintain a thriving cool water fishery. The result is a range of recommended monthly flows and daily flow guidance illustrating the advantage of combining a wide range of available disciplinary information, supplemented by judgment based on ecological principles and a general understanding of river ecosystems, in a highly altered, working river. ?? 2010 American Water Resources Association.