The evolutionary process of readaptation to the aquatic environment was accompanied by extreme anatomical and physiological changes in the brain. This review discusses cortical specializations in the three major lineages of marine mammals in comparison to related terrestrial and semiaquatic species. Different groups of marine mammals adopted a wide range of strategies to cope with the challenges of aquatic living. Cetaceans and hippopotamids possess a completely agranular neocortex in contrast to phocids and sirenians; vertical modules are observed in deep layers V and VI in manatees, cetaceans, phocids, and hippopotamids, but in different cortical areas; and clustering in layer II appears in the insular cortex of hippopotamids, phocids, and cetaceans. Finally, von Economo neurons are present in cetaceans, hippopotamids, sirenians, and some phocids, with specific, yet different, cortical distributions. The interpretation of the evolutionary and functional significance of such specializations, and their relationships with the degrees of adaptation to the aquatic environment and phylogeny, remain difficult to trace, at least until comprehensive data, including representative species from all of the major mammalian families, become available.