The Mediterranean region is increasingly affected by water scarcity because of rising demand (population growth and land-use changes) and decreasing availability (Climate change led rainfall decreases). This situation leads to an increasing proportion of temporary waterways (defined as waterways that cease to flow at some points in space and time along their course, as well as to the depletion of aquifers. Water scarcity has a dramatic impact on ecosystem health, hydrology, river chemistry, and those economic sectors that strongly rely on water availability such as agriculture and tourism (70% of available worldwide freshwater is used in irrigated agriculture). The worst-case scenario is encountered in the regions of southern Mediterranean area, which are characterized by high spatial and temporal imbalances of water demand and availability, seasonal water uses, and inadequate water resources management. Therefore, in order to supply water to human settlements in arid or semi-arid countries the over-exploitation of water resources is common. Non-sustainable practices are globally widespread and manifest themselves in the over pumping of aquifers, seawater intrusion, river flows composed mainly by wastewater, and the salinization of irrigated soils. To counteract these trends, many research and policy initiatives have been launched to better estimate water resources, ecological status or ecosystem services in the Mediterranean region, as well as initiatives to foster integrated water management. However, none of those has put all these pieces together to solve this puzzle and to support decision-makers in the struggle they face in reconciling the various demands on decreasing water resources.