The rewarding effects of drugs of abuse have been linked to increases in dopamine transmission. However, changes in brain chemistry and morphology that are produced in addiction underlie the long-lasting vulnerability to relapse and are more closely linked with the adaptations in excitatory transmission. The drug-induced changes in excitatory transmission seem to be pathologic exacerbations of normal forms of brain plasticity, and they occur in the brain areas linked by neuroimaging studies in addicted patients to craving and relapse. This review describes the brain adaptations produced in excitatory transmission by addictive drugs and identifies new potential sites of pharmacotherapeutic intervention to ameliorate addiction.