An observational analysis of Mediterranean Sea water cycle variability based on recently available datasets provides new insights on the long-term changes that affected the region since the 1960s. Results indicate an overall increase in evaporation during 1958–2006, with a decrease up until the mid-1970s and an increase thereafter. Precipitation variability is characterized by substantial interdecadal variations and a negative long-term trend. Evaporation increase, primarily driven by SST variability, together with precipitation decrease resulted in a substantial increase in the loss of freshwater from the Mediterranean Sea toward the overlying atmosphere. An increase in the freshwater deficit is consistent with observed Mediterranean Sea salinity tendencies and has broad implications for the Mediterranean water cycle and connected systems.These observational results are in qualitative agreement with simulated Mediterranean Sea water cycle behavior from a large ensemble of models from the Coupled Model Intercomparison Project Phase 3 (CMIP3). However, simulated anomalies are about one order of magnitude smaller than those observed. This inconsistency and the large uncertainties associated with the observational rates of change highlight the need for more research to better characterize and understand Mediterranean water cycle variations in recent decades, and to better simulate the crucial underlying processes in global models.