The concept of differentiation of self entails two primary aspects based on the observations of Dr. Bowen. The first is that individuals vary in the degree to which they differentiate or develop emotional autonomy in relation to the family in which they grew up. The second aspect is the degree to which an individual’s higher cortical systems, referred to by Bowen as the intellectual system, differentiate over the course of development. The differentiation of this function underlies an individual’s capacity to utilize the intellectual system in self-regulation and self-direction over their life course. This presentation will describe the above and place these processes in the context of the co-evolution of the family and the brain.