This review has focused on neurochemical systems and brain circuits that are relevant for alcohol addiction from the perspective of motivation and reinforcement. Ethanol alters synaptic transmission by modulating neuronal excitability through an interaction with ligand and voltage-gated ion channels. As a result, alcohol directly or indirectly affects the function of many neurotransmitter systems in the brain. These actions, and in particular the actions at GABAA, NMDA, and serotonin 5-HT3 ionotropic receptors, are of central importance for the addictive effects of ethanol in addition to interactions with the neurochemical systems discussed here. As reviewed elsewhere, important advances have been made in the understanding of the mechanisms of these actions by ethanol and their relevance for alcohol intoxication, tolerance, dependence, and withdrawal (Grant and Lovinger, 1995; Woodward, 2000; Morrow et al., 2001). Understanding the integration of the interactions among these multiple systems in the regulation of ethanol-seeking behavior and the development of ethanol dependence is an important challenge for future research.