Hydroelectric power is playing a new and often expanded role in the world’s major power grids, offering low carbon generating capacity in industrializing, dam-building economies while providing reserve and flexibility to co-manage fledgling wind and solar resources in high income countries. Driven by river flows, conventional hydropower is exposed to the vagaries of weather and climate, motivating drought and climate change hydropower impact studies at large spatial scales. Here we review methods of climate-driven hydropower simulation at large spatial scales, specifically multi-basin regions to global. We identify four types of approach based on complexity of tools and richness of data applied to the problem. Since the earliest attempts to model climate-driven hydropower at continental scale almost two decades ago, the field has transitioned from one of scientific curiosity to practical application, with studies increasingly motivated by the need to inform power grid expansion planning and operation. As the hydrological and water management models used in large-scale hydropower studies become more sophisticated, new opportunities will emerge to study the impacts of changing hydropower on power system reliability and performance at large power grid scale. To grasp these opportunities, the water resources community must continue to enhance data and models for representing river flows and anthropogenic water use and management at subcontinental to global scales.