David W. SelfThe last decade has witnessed the emergence of new pharmacotherapy in the treatment of drug and alcohol dependence, although addiction to the psychostimulants cocaine and amphetamines is notoriously resistant to pharmacological approaches that can effectively promote abstinence (). Development of new approaches to treatment that are derived from a deeper understanding of the pathogenesis of addiction is long overdue, but some evidence-based treatment strategies are promising. These treatments have relied, in part, on animal models capable of tracking changes in drug responsiveness after repeated exposure and more sophisticated animal models that capture the transition from initial drug use to a high degree of drug dependence. The neurobiological changes that accompany these behavioral changes are thought to enhance the motivation to self-administer drugs and alcohol and underlie the propensity for relapse over prolonged periods despite sincere efforts to abstain. Many of the neurobiological changes discovered using these animal models are common to multiple classes of abused drugs and alcohol, raising the exciting possibility that treatments designed to ameliorate these changes would have broad therapeutic impact in the treatment of addiction.