The efficient use of water supplies requires a systems approach that encompasses all aspects of making water available and its use within society that must recognise global issues. Increasing the efficiency of water use within agricultural systems is an essential priority in many regions including the Mediterranean. This review examines the research priorities, the prospects for crop and soil management and plant breeding and biotechnology that are needed to achieve high stable yield under drought in the Mediterranean. Research must combine the latest genomics resources including quantitative genetics, genomics and biomathematics with an ecophysiological understanding of the interactions between crop plant genotypes and the growing environment to better inform crop improvement.