This article argues that the shift from the bipolar structure of the Cold War international system to a more polycentric power structure at the system level has increased the significance of regional relations and has consequently enhanced the importance of the study of regionalism. It makes a case for a Mediterranean region and examines various efforts aimed at defining what constitutes a region. In so doing, it investigates whether the Regional Security Complex Theory (RSCT) can be utilized to define a Mediterranean region and argues that the patters of amity and enmity among Mediterranean states are necessary but not sufficient to identify such a region. It suggests that economic, energy, environmental, and other factors, such as migration and refugee flows should be taken into consideration in order to define the Mediterranean region. It also claims that the Mediterranean security complex includes three sub-complexes. The first is an eastern Mediterranean sub-complex that revolves mainly - albeit not exclusively - around three conflicts: the Greek-Turkish conflict, the Syrian conflict, and the Israeli-Palestinian/Arab conflict. The second is a central Mediterranean sub-complex that includes Italy, Libya, Albania and Malta and which revolves mainly around migration with Italy playing a dominant role due to its historical ties to both Libya and Albania. The third is a western Mediterranean security sub-complex that includes France, Algeria, Tunisia, Morocco, Spain and Portugal. This sub-complex it centered around France, the migration question and its associated threats, such as terrorism, radicalism, and human trafficking. In conclusion, it is concluded that the Mediterranean security complex is very dynamic as there are states (i.e. Turkey) that seem eager and capable of challenging the status quo thereby contributing to the process of the complex’s internal transformation.