NMDA receptors are glutamate-gated ion channels, mediating excitatory neurotransmission in the brain. These widely distributed receptors are known to play a role in neuronal development and synaptic plasticity, but over stimulation of these receptors can lead to neurotoxicity. In recent years, NMDA receptors have emerged as an important site of action of ethanol. It is believed that at least some of the deleterious effects of ethanol like alcohol dependence, development of tolerance to alcohol and alcohol withdrawal syndrome are mediated via NMDA receptors. The sensitivity of NMDA receptors to ethanol, however, varies regionally. This diversity of NMDA receptor sensitivity is believed to result, at least in part, from heterogeneity of receptor subunit composition. Ethanol's effects on NMDA receptors, including alteration in receptor function and number, probably result from interplay of multiple mechanisms some of which are discussed here.