Status quo water scarcity in the Mediterranean region is expected to be exacerbated as hydro-climatic changes intensify, demanding the development of place-based interventions with careful attention to contextualized economic, environmental, social, and institutional interactions. Key to this will be advancement of contemporary understanding of the combined influences of climate and human activity changes on water availabilityWater availability in the region, in particularly considering that decreases in precipitation may be up to 30%, while increases in mean annual temperature may be 20% above the global average, and given the influence of these factors on the nexus of water sand food security. Freshwater use by and supply to the general population and particular sectors, such as agriculture and tourism, is of particular concern during summer with elevated water demands coupled and reduced replenishment of water supplies. The development of effective and sustainable water management practices to reduce excessive summer-time water demands will be key to the future prosperity, productivity, and longevity of critical sectors including agriculture. Water supply is also threatened by quality deterioration, e.g., by eutrophication of water reservoirs and groundwater contamination by excess nitrogen and salinity. In this chapter, we explore trends in water availabilityWater availability, demand, links with land use, and issues associated with water quality. We further discuss opportunities to improve water availabilityWater availability and food security with coordinated management strategies for: (i) increasing freshwater availabilityWater availability by enhancing storage capacity, rainwater harvesting, and potential inter-basin water transfers; (ii) use of non-freshwater resources, such as desalination, treated wastewater and graywater reuse, and (iii) decreasing water demands. Comprehensive knowledge of the spatial and temporal status of water resources and key water securityWater security challenges can support decision-making and guide water management in the region.