In order to elucidate the evolutionary origin and process of the brain and central nervous system (CNS), we took an approach of making genomic comparisons of a protein-coding gene set between human and other species. In practice, we first obtained about 400 protein-coding genes whose level of the mRNA expression is more than 50% in a human brain or CNS compared with those in other tissues or organs in the H-ANGEL (Human-Anatomical Gene Expression Library) section of the H-Invitational integrated database of human genes. We now call those genes operationally as “human nervous system-specific genes (human NS-specific genes).” We, then, compared these human NS-specific genes with the protein-coding genes that were contained in each of the entire genome of the species available, in order to estimate when each of the human NS-specific genes emerged during evolution. As a result, we found that about one thirds of the human NS-specific genes evolutionarily emerged just before the outbreak of bony fish. It follows that there was a kind of explosive emergence of NS-specific genes just before evolutionary appearance of bony fish, leading to initial formation of a complex and integrated brain and CNS. Moreover, we also examined the genes expressed in a planarian head by use of the EST analysis of about 25,000 gene clones and the so-called gene chip, because the planarian is known as having the most primitive brain. As a result, we obtained about 120 genes that were specifically expressed in a planarian head. We, then, found that a majority of those genes had shared strong sequence homologies with human genes, suggesting that the genes potentially forming the human brain have already existed as the ancestral genes. We also examined about 250 genes specifically expressed in the neural cells and motion-controlling cells of hydra which does not have any central nervous system, by making a chip of about 6,500 hydra genes. We found that a half of those genes appeared to share the known functions with higher organisms including human. Thus, I would discuss the evolutionary origin and process of the brain and central nervous system, taking into account those genes that are expressed in the neural systems of those primitive organisms.