The operation of the power systems is constrained by the availability of water resources, which are necessary for cooling thermal power plants and determine the generation of hydro reservoirs and run-of-river power plants. The interactions between the water and power systems have impacts on the quantity and quality of the water resources, thus affecting human uses and the environment. The European power system has witnessed in the past several examples of the consequences of reduced availability of water, which range from monetary losses, to demand restrictions, or increased wear and tear of the power plants. The importance of these impacts, and the expectation that climate change will produce similar episodes in the future more often, raises several research questions relevant for policy making. Some of these questions may be addressed by WATERFLEX, an exploratory research project carried out by units C7 (Knowledge for the Energy Union) and D2 (Water and Marine Resources) of the European Commission’s Joint Research Centre (JRC). The main goal of WATERFLEX is to assess the potential of hydropower as a source of flexibility to the European power system, as well as analysing the Water-Energy nexus against the background of the EU initiatives towards a low-carbon energy system. The method proposed in the WATERFLEX project for better representing and analysing the complex interdependencies between the power and water sectors consists of combining two of the modelling tools available at the JRC, the LISFLOOD hydrological model and the Dispa-SET unit commitment and dispatch model , with a medium-term hydrothermal coordination model. In order to test and validate the proposed approach described above, this document describes a case study carried out to analyse the implications of different hydrologic scenarios for the flexibility of the Greek power system.