This chapter reviews the neuroanatomy and circuits implicated in the pathophysiology of substance related and addictive disorders. Its goal is first to review current understanding of the neural systems believed to underlie the specific clinical hallmarks of substance use disorders, introducing these systems in a manner that emphasizes their evolving roles and relative significance/contributions over the clinical trajectory from initial controlled/volitional to severe compulsive pursuit and consumption. Next, it reviews our understanding of the impact of sustained substance use on these circuits and the challenges they pose for durable recovery. Finally, briefly, it reviews neuroanatomic correlates/predictors of risk and resilience in early substance use, as well as relapse risk in recovery.