Evidence is presented to show that multiple neurotransmitter systems of the brain reward systems including GABA, glutamate, dopamine, serotonin and opioid peptides are involved in alcohol reinforcement. Dependence is associated with changes in many of these same systems, but also with changes in other neurotransmitters, such as brain corticotropin releasing factor. A midbrain forebrain circuitry that involves parts of the nucleus accumbens and amygdala is hypothesized to be the focus for the neuropharmacology of alcohol reinforcement.