During the last years, a great effort is being made from the scientific community to study the sensitivity of regional climate models to specific parameterizations. Numerous studies have been made regarding that field of research; however, it has not been widely applied in Europe. Thus, it was essential to study the sensitivity of regional climate models to the different physics parameterization schemes in the Mediterranean region. The examined regional climate model used in this study is RegCM4.4.5.1. Its spatial resolution is 25x25km. Different simulations were performed with changes in the model’s physics parameterization schemes for the time period 1981-1990. In order to “run” RegCM4, ERA-Interim data for initial and boundary conditions (ICBC) and sea surface temperature (SST) were utilized. For the examination of the sensitivity of the regional climate model to the different physics configurations of the model, the different simulated data of temperature and precipitation were processed on a seasonal basis and the differences between the simulations were calculated, mapped and compared. The statistical significance of the differences is calculated with Student’s t-test. Aiming a more detailed simulation of the changes that occur, a division of the area of study in five sub-regions was performed according to the common EURO-CORDEX analysis domain and the Taylor diagrams for the examined parameters were calculated. This study is a first attempt to find the best combination of parameterizations to “run” RegCM4 for the domain of interest and finally to perform a dynamical downscaling of the regional climate model in order to produce the best possible projections for future climate in the Greek area.