The effects of continued global warming on water resources are a concern for water managers and stake holders. In the western United States, where the combined climatic demand and consumptive use of water is equal to or greater than the natural supply of water for some locations, there is growing concern regarding the sustainability of future water supplies. In addition to the adverse effects of warming on water supply, another issue for water managers is accounting for, and managing, the effects of natural climatic variability, particularly persistently dry and wet periods. Analyses of paleo-reconstructions of Upper Colorado River basin (UCRB) flow demonstrate that severe sustained droughts, and persistent pluvial periods, are a recurring characteristic of hydroclimate in the Colorado River basin. Shifts between persistently dry and wet regimes (e.g., decadal to multi-decadal variability (D2M)) have important implications for water supply and water management. In this study paleo-reconstructions of UCRB flow are used to compute the risks of shifts between persistently wet and dry regimes given the length of time in a specific regime. Results indicate that low frequency variability of hydro-climatic conditions and the statistics that describe this low frequency variability can be useful to water managers by providing information about the risk of shifting from one hydrologic regime to another. To manage water resources in the future water managers will have to understand the joint hydrologic effects of natural climate variability and global warming. These joint effects may produce future hydrologic conditions that are unprecedented in both the instrumental and paleoclimatic records.