The orbitofrontal cortex (OFC) plays a central role in human behavior. Anatomically connected with association areas of all sensory modalities, limbic structures, prefrontal cortical regions that mediate executive function and subcortical nuclei, this brain region can serve to integrate the physical and emotional attributes of a stimulusobject and establish a motivational value based on estimation of potential reward. To the extent that addictive disorders reflect a dysregulation of the ability to evaluate potential reward against harm from drug self-administration, it would be anticipated that substance abuse disorder might reflect dysfunction of the OFC. With the application of brain imaging techniques to the study of human substance abuse, evidence has been obtained that activity in the OFC and its connections plays a role in several components of the maladaptive behavior of substance abuse, including expectancy, craving and impaired decision making.