This paper is the outcome of a workshop held in Rome in November 2011 on the occasion of the 25th anniversary of the POEM (Physical Oceanography of the Eastern Mediterranean) program. In the workshop discussions, a number of unresolved issues were identified for the physical and biogeochemical properties of the Mediterranean Sea as a whole, i.e., comprising the Western and Eastern sub-basins. Over the successive two years, the related ideas were discussed among the group of scientists who participated in the workshop and who have contributed to the writing of this paper.