The impact of climate change on the hydrological regime and water resources in the basin of Venetikos river, in Greece is assessed. A monthly conceptual water balance model was calibrated in this basin using historical hydro meteorological data. This calibrated model was used to estimate runoff under a transient scenario (UKTR) referring to year 2080. The results show that the mean annual runoff, mean winter and summer runoff values, annual maximum and minimum values, as well as, monthly maximum and minimum, will be reduced. Additionally, an increase of potential and actual evapotranspiration was noticed due to temperature increase.