Joint research between economists and hydrologists increasingly contributes to optimising the economic value gained from water, while safeguarding its social and environmental values. The application of hydro-economic analysis to mining regions, however, is limited. This paper examines why this is the case and how to confront it. The paper focuses on identifying and describing features of large-scale mines and mine regions that are challenging to analyse such as: magnitude of capital involved, time-scale and remoteness of projects, inherent environmental risks, and strong negative perceptions about mining's impacts on water. These characteristics may limit the applicability of established hydro-economic concepts and methods, thus risk-based metrics are discussed as complementary tools. We also contend that further research and development in water-related ecosystem services should be a priority, in order to better quantify trade-offs between the economic benefits of water use by mining and competing users, including environmental flows. Case studies of mining regions in Chile, Madagascar and Sweden are summarised to illustrate some of the issues raised. While data limitations are an obstacle, new and extended case studies are required to explore how the challenges may be addressed.