Many current assessments of future climate and hydrologic change suggest that current drylands around the globe could become drier with continued anthropogenic climate change. In some regions, such as the southwest U.S., there is an observed trend in this direction. This is particularly true for the Colorado River, where the nature of drought is shifting to a more temperature-dominated climate extreme. At the same time, however, some recent and influential scientific assessments suggest that temperature-driven drying could be compensated by precipitation increases with little net increase to water supply or ecosystem risk. A new approach integrating the examination of temperature, precipitation and drought risk indicate that Colorado River flows, water supplies, and ecosystems in the Southwest are already being seriously affected by warming, and that continued warming could result in much larger water supply losses than widely thought, even if mean precipitation increases. The implications of these results have serious implications for terrestrial systems in many parts of the globe, including regions with higher average precipitation (e.g., the Amazon and Great Lakes regions). Interestingly, we may be able to say this with high confidence.