N-methyl-D-aspartate receptors belong to the family of ionotropic glutamate receptors. NMDA receptors were named after the specific glutamate-like synthetic agonist N-methyl-D-aspartate. In the past decade, an increasing number of functional sites have been discovered and used to refine the operational definition of NMDA receptors. The goal to characterize the molecular substrate underlying the heretofore strictly operationally defined NMDA receptors has come into reach following the cloning of a number of cDNAs coding for NMDA receptor subunits. However, in their review, Nikolaus Sucher and colleagues show that caution should be exercised in comparing the pharmacological properties of recombinant NMDA receptors to those of native neurones. Future work on NMDA receptors will be challenged to reconcile disparate effects obtained with recombinant versus native receptors.