The importance of glutamate in the reinstatement of cocaine-seeking behavior has been established. New molecular and neurochemical adaptations in the glutamatergic system which drive cocaine relapse have been identified, such as the ability of CB1 receptor stimulation to reduce basal glutamate levels and the involvement of the GluR1 receptor subunit in reinstatement. Furthermore, it is apparent that similar glutamatergic neuroadaptations arise after self-administration of cocaine, heroin, nicotine, and alcohol. For example, reinstatement to cocaine, nicotine, and alcohol can be prevented both by the stimulation of group II mGluR receptors and by the blockade of group I mGluR receptors. The similarities in the neurochemistry behind relapse to these varied drug classes indicate that drugs that target the glutamate system could be effective at treating relapse to multiple types of drugs.