Abstract While genetic and environmental factors are known to male substantial contributions to the pathogenesis of physical disease, the role of the brain in these processes is largely unknown. It is hypothesized that the manner in which the brain is functionally organized is an integral factor in physical health outcomes, both positive and negative. It is further hypothesized that changes in certain patterns of the functional organization of the brain play a significant role in the pathogenesis of physical disease, mediating between an individual's genetic endowment, the environment, and other relevant brain systems to initiate, modulate and/or maintain these disorders. There are many currently available treatment modalities which have the capacity to change the pattern of functional brain organization. Such interventions have the potential to become valuable aids in both the treatment and prevention of physical disease.