Despite being a natural phenomenon, water scarcity is, to a great extent, human-induced, particularly affected by climate change and by the increased water resources vulnerability. The Water Framework Directive (WFD), an ‘umbrella’ directive that aims to provide holistic approaches to the management of water resources and is supported by a number of Communication documents on water scarcity, requires for prompt responses to ensure ‘healthy’ water bodies of good ecological status. The current paper presents a multidisciplinary approach, developed and engaged within the Globaqua Project, to provide an assessment of the main challenges towards addressing water scarcity with emphasis on the climate change projections, in two Mediterranean regions. The current paper attempts to critically assess the effectiveness of the WFD as a tool to address water scarcity and increase sustainability in resource use. Criticism lies on the fact that the WFD does not directly refer to it, still, water scarcity is recognized as a factor that increases stress on water resources and deteriorates their status. In addition, the Program of Measures (PoMs) within the WFD clearly contribute to reducing vulnerability of water resources and to ensure current and future water use, also under the impact of the projected climate change.