NMDA receptors are a multi-subunit family of ionotropic receptors activated by the neurotransmitter glutamate. Localized primarily postsynaptically in neurons, they play an important role in mediating excitatory synaptic neurotransmission and are implicated in a wide variety of important calcium-dependent neuronal processes. Experimental animals expressing mutant forms of NMDA subunits display abnormal behaviors and locomotor and cognitive impairments. Over the last 10 years, a wealth of studies has indicated that NMDA receptors are an important site of action for ethanol in the brain. The effects of acute ethanol on NMDA receptor function is discussed herein, with particular focus on efforts to define a molecular site of action of ethanol on the receptor. While it is clear that the ethanol sensitivity of NMDA receptors is influenced by subunit composition, it is also apparent that posttranslational factors such as phosphorylation and protein-protein interactions are important in modulating this sensitivity.