The climatic and hydrological systems are tightly related and any induced changes cause chained interactions. In an attempt to adequately manage water resources in Greece, a series of experiments were conducted with different GCMs in selected study areas to understand this interplay. This paper is an overview of the studies carried out in the Aliakmon, the Upper Acheloos, the Portaikos, and the Pinios basins, where the regional hydrological cycle was evaluated on river basin spatial scale to assess regional impacts and variability. The impacts of climate change on the water resources are presented in a synthetic quantitative way, in order to draw general conclusions concerning the trends of the hydrological indicators. A good agreement was observed between the different climatic experiments, and the trends on the selected hydrological indicators demonstrate an increase in temperature and PET, reduction in the mean annual precipitation and runoff, and a shifting of the snowmelt period towards the winter, while the snowpack storage was proved to be a controlling factor. It is accentuated that relatively small decreases in the mean annual precipitation cause dramatic increase of reservoir risk levels of annual firm water supply and energy production. As a result, radical increases of reservoir storage volume are required to maintain firm water and energy yields at tolerable risk levels. The adaptive capacity of the country is not that high, and a series of serious actions need to be taken in order to mitigate the effects of climate change and assess its impacts.