The aim of the present study was to review the available literature on the evolutionary processes that have led to the development of the human central nervous system (CNS) cholinergic system and to test the hypothesis that such processes may have contributed to the emergence of psychiatric diseases. First, it is clear that the molecular components that have come together to form the cholinergic system in the human CNS initially had functions that were not involved in neurotransmission. Indeed, components of the cholinergic system of the human CNS may be present in nearly all forms of life and may have existed since life began. Significantly, components of the human CNS cholinergic system had begun to interact with each other millions of years ago, long before the appearance of any nervous system. Moreover, there are data to suggest that changes in the mammalian CNS cholinergic system can involve involved gene and environment interactions. Evidence is available to support the notion that the changes in functioning of the human CNS cholinergic system in individuals with psychiatric disorders may have resulted from both Darwinian and Lamarckian concepts of evolution.