The Mediterranean basin has been identified as one of the world's regions most vulnerable to climatic and anthropogenic changes. A methodology accounting for the basin specific conditions is developed to assess the impacts of these changes on water resources. Based on global climate projections and water-use scenarios inspired by national reports, the current water stress state is addressed first and then it is explored for the medium term. Currently, the southern and eastern rims are experiencing high to severe water stress. By the 2050 horizon, this stress could increase over the whole Mediterranean basin, notably because of a 30-50% decline in freshwater resources as a result of climate change. In addition, under a business-as-usual water-use scenario, total water withdrawals are projected to double on the southern and eastern rims. These worrying trends indicate the need to develop mitigation scenarios. In accord with the Mediterranean Strategy for Sustainable Development, an alternative water-use scenario based on improvements in the efficiency of water distribution networks and of irrigated agriculture is investigated. Such progress would stabilize total water withdrawals over the Mediterranean basin and even make them decrease (10-40%) in many northern catchments. Water stress could thus be tempered in some eastern catchments and remain low on the northern rim. This study highlights the importance of developing sustainable development strategies to cope with climatic and anthropogenic changes in order to explore their impacts at regional scales. It supports the need to focus on the most vulnerable areas within the Mediterranean basin.