The midfrontal cortex, and particularly the anterior cingulate gyrus, appears active in many studies of functional imaging. Various models have competed to explain the functions of the anterior cingulate in relation to its patterns of activation. We believe that the concept of self-regulation is valuable in considering the role of the cingulate. The sensitivity of the cingulate to both reward and pain, and evidence for cingulate coupling to cognitive and emotional areas during task performance, support this identification. Self-regulation is a very broad concept that does not lend itself very well to specific models or tests, but it does provide a framework for examining development. We trace the role of the midfrontal cortex in evolution and infant development. Both genes and environment influence self-regulation. The presence of both genetic and environmental effects raises the issue of their interaction, which we discuss in relation to the dopamine 4 receptor gene and parenting methods. The role of the midfrontal cortex in self-regulation allows us to consider both brain networks common to all people and network efficiency underlying individual differences in behavior.