The importance of the Mediterranean Sea for the world ocean has long been recognized. First, the Mediterranean sea has a profound impact on the Atlantic ocean circulation and, consequently, on the global thermohaline conveyor belt. Maps of the Mediterranean salty water tongue exiting from the Gibraltar strait at intermediate depths and spreading throughout the Atlantic interior are well known since the 1950s. Through direct pathways to the Atlantic polar regions or through indirect mixing processes, the salty Mediterranean water preconditions the deep convection cells of the polar Atlantic. There the North Atlantic Deep Water is formed which successively spreads throughout the world ocean constituting the core of the global thermohaline circulation. Even more importantly, the Mediterranean Sea is a laboratory basin for the investigation of processes of global importance, being much more amenable to observational surveys because of its location in mid-latitude and its dimensions. Both the western and eastern basins in fact possess closed thermohaline circulations analogous to the global conveyor belt. A unique upper layer open thermohaline cell connects the eastern to the western basin and, successively, to the north Atlantic through the Gibraltar strait. In it, the Atlantic water entering into Gibraltar in the surface layer, after travelling to the easternmost Levantine basin, is transformed into one of the saltiest water masses through air–sea heat and moisture fluxes. This is the salty water which, crossing the entire basin in the opposite direction below the surface Atlantic water, finally exits from the Gibraltar strait at mid-depths. Both the western and eastern basins are endowed with deep/intermediate convection cells analogous to the polar Atlantic deep convection cells or to the intermediate mode water ones. Deep and intermediate water masses are therefore formed in different sites of the entire basin. Because of their easily accessible locations, these convection cells are much more amenable to direct observational surveys and mooring arrays. An ubiquitous, energetic mesoscale and sub-mesoscale eddy field is superimposed to and interacts with the sub-basin scale, wind-driven gyres that characterize the upper thermocline circulation. Three different scales of motion are therefore superimposed producing a richness of interaction processes which typify similar interactions in unexplored ocean regions. Both wide and narrow shelves are present separated by steep continental slopes from the deep interiors. Cross-shelf fluxes of physical as well biogeochemical parameters are crucial in determining the properties of the shallow versus deep local ecosystems and their trophic chain. Most importantly, the Mediterranean Sea is a basin of contrasting ecosystems, from the strongly oligotrophic deep interiors to the fully eutrophic northern Adriatic characterized by recurrent, anomalous algal blooms and related anoxia events. This review focuses on the identification of the major unresolved scientific issues and wants also to provide directions for future research which may lead to the formulation of interdisciplinary, collaborative implementation plans to address these issues both theoretically and observationally.