Cultures in Mediterranean climate zones (MCZs) around the world have long been reliant on groundwater and springs as freshwater sources. While their ecology and cultural sustainability are recognized as critically important, inter-relationships between springs and culture in MCZs have received less attention. Here we augmented a global literature review with case studies in MCZ cultural landscapes to examine the diversity and intensity of cultural and socio-economic relationships on spring ecohydrogeology. MCZs are often oriented on western and southern coasts in tectonically active landscapes which control aquifer structure, the prevalence of westerly winds, and aridity, and generally expose associated habitats and cultures to harsh afternoon sunlight. Cultural appreciation and appropriation of springs ranges widely, from their use as subsistence water supplies to their roles in profound traditions such as Greco-Roman nymphalea as well as Asian and Abrahamic spiritual cleansing and baptism. The abandonment of traditional ways of life, such as rural livestock production, for urban ones has shifted impacts on aquifers from local to regional groundwater exploitation. The commoditization of water resources for regional agricultural, industrial (e.g., mining, water bottling, geothermal resorts), and urban uses is placing ever-increasing unsustainable demands on aquifers and spring ecosystems. When the regional economic value of springs approaches or exceeds local cultural values, these irreplaceable aquatic ecosystems are often degraded, over-looked, and lost. Sustainable stewardship of springs and the aquifers that support them is a poorly recognized but central conservation challenge for modern Mediterranean societies as they face impending impacts of global climate change. Solutions to this crisis require education, societal dialogue, and improved policy and implementation.