The pleasant effects of food and alcohol intake are partially mediated by mu-opiate receptors in the ventral striatum, a central area of the brain reward system. Dopamine release, on the other hand, was associated with attribution of incentive salience to reward-predicting stimuli. Once excessive alcohol consumption is established, GABAergic and glutamatergic neuroadaptation underlie tolerance development and withdrawal symptoms. Combined functional brain imaging studies and studies wit positron emission tomography suggest that in the brain reward system, neuroadaptation in dopaminergic and opioidergic neurotransmission seems to augment neuronal responses to well-established, alcohol-associated stimuli while interfering with the acquisition of new, reward-seeking behavior patterns. In imaging studies with positron emission tomography, the availability of central mu-opiate receptors was measured with the radioligand carbon 11-labeled carfentanil in the ventral striatum of alcoholics and controls matched for mu-opiate receptor genotype. An increased availability in the ventral striatum, the core area of the brain reward system, and in the medial prefrontal cortex was found in alcoholics correlated with the severity of alcohol craving as assessed by the Obsessive Compulsive Drinking Scale (OCDS). Dysfunction of dopaminergic and opioidergic neurotransmission may contribute to alterations in positive and negative affect. In detoxified alcoholics, a high brain activity elicited by affectively positive cues was associated with a reduced relapse risk and may thus provide a protective factor that could be influenced by psychotherapy or additive medication.