During the Cenomanian-Turonian interval, marine squamates display a spectacular radiation in particular on the margins of the Mediterranean Tethys and, to a lesser extent, in the Interior Seaway of North America. In this span of time, three major groups diversified: the “hind-limbed” snakes (“pachyophiids”), the “dolichosaurids”, and the mosasauroids. “Hind-limbed” snakes, exhibiting all a pachyostotic bony structure, were small tropical inhabitants, known exclusively from the Cenomanian of the Mediterranean Tethys. “Dolichosaurids” and mosasauroids were rather mid latitude distributed groups, found in a wide range of palaeoenvironments of both the Mediterranean Tethys and the Western Interior Seaway. Whereas “dolichosaurids” remain of small size and become rare after the Cenomanian/Turonian (C/T) boundary, mosasauroids exhibit a notable size-increase and develop since the mid Turonian to become highly diversified and cosmopolitan large predators of the end of the Cretaceous. This important radiation of marine squamates is thus, except for derived mosasauroids (mosasaurids), restricted in time (Cenomanian-Turonian) and space (mostly the northern and southern margins of the Mediterranean Tethys). It is probable that: 1) the Mediterranean Tethys played an important role in both the radiation and the dispersion of these marine squamates during the Cenomanian-Turonian interval; 2) certain major geological and biological events that characterize this pivotal period (i.e., global high sea-level stand and warm sea-surface temperatures allowing the development of large carbonated platforms) could have permitted this radiation; and 3) conversely, other factors occurring at or just after the C/T boundary (OAE2, sea-level and sea-surface temperature drops, marine extinctions including the demise of carbonated platforms) as well as factors inherent to each of the groups (mainly the size and bone microstructure) could have had an effect on and insured the success of the mosasaurids with respect to the other groups, whereas thereafter the radiation of snakes succeeded only in continental environments.