Climate change is bringing more risk and uncertainty to water management in the world’s Mediterranean-climate regions. In this paper, we compare two Mediterranean-climate watersheds: the Durance basin in southern France, and the Sacramento River in northern California, USA. For the Durance basin, we present new research on climate change impacts on water management, and discuss their implications for potential adaptation responses. For the Sacramento River, we review existing climate data and research on impacts and describe the progress in implementing various adaptation strategies. We find that the Durance and Sacramento—while certainly at different scales—nonetheless share many characteristics, such as a highly variable climate and hydrology, and extensive hydromodification and intense water competition, which will be affected by climate change. Although some issues and approaches to adaptation are unique to each region, at the same time, these two river basins are utilizing some similar strategies to cope with a changing climate, such as regional planning and management and water conservation.