The adaptation of cetaceans to a fully aquatic lifestyle represents one of the most dramatic transformations in mammalian evolutionary history. Two of the most salient features of modern cetaceans are their fully aquatic lifestyle and their large brains. This review article will offer an overview of comparative neuroanatomical research on aquatic mammals, including analyses of odontocete cetacean, sirenian, pinniped, and fossil archaeocete brains. In particular, the question of whether a relationship exists between being fully aquatic and having a large brain is addressed. It has been hypothesized that the large, well-developed cetacean brain is a direct product of adaptation to a fully aquatic lifestyle. The current consensus is that the paleontological evidence on brain size evolution in cetaceans is not consistent with this hypothesis. Cetacean brain enlargement took place millions of years after adaptation to a fully aquatic existence. Neuroanatomical comparisons with sirenians and pinnipeds provide no evidence for the idea that the odontocete's large brain, high encephalization level, and extreme neocortical gyrification is an adaptation to a fully aquatic lifestyle. Although echolocation has been suggested as a reason for the high encephalization level in odontocetes, it should be noted that not all aquatic mammals echolocate and echolocating terrestrial mammals (e.g., bats) are not particularly highly encephalized. Echolocation is not a requirement of a fully aquatic lifestyle and, thus, cannot be considered a sole effect of aquaticism on brain enlargement. These results indicate that the high encephalization level of odontocetes is likely related to their socially complex lifestyle patterns that transcend the influence of an aquatic environment. Anat Rec, 290:694–700, 2007. © 2007 Wiley-Liss, Inc.