A negative allometric relationship between body mass (BM) and brain size (BS) can be observed for many vertebrate groups. In the past decades, researchers have proposed several hypotheses to explain this finding, but none is definitive and some are possibly not mutually exclusive. Certain species diverge markedly (positively or negatively) from the mean of the ratio BM/BS expected for a particular taxonomic group. It is possible to define encephalization quotient (EQ) as the ratio between the actual BS and the expected brain size. Several cetacean species show higher EQs compared to all primates, except modern humans. The process that led to big brains in primates and cetaceans produced different trajectories, as shown by the organizational differences observed in every encephalic district (e.g., the cortex). However, these two groups both convergently developed complex cognitive abilities. The comparative study on the trajectories through which the encephalization process has independently evolved in primates and cetaceans allows a critical appraisal of the causes, the time and the mode of quantitative and qualitative development of the brain in our species and in the hominid evolutionary lineage.