The glutamate-binding sites of ionotropic glutamate receptors are formed from two extracellular domains of a single subunit. Conformational changes induced by agonist binding produce mechanical processes that are translated into ion gating and receptor desensitization. The interactions between macromolecular assemblies of synaptic proteins and ionotropic glutamate receptors, and their subsequent roles in receptor clustering and specificity are being elucidated. Kainate receptor pharmacology is finally revealing its secrets as a result of the availability of selective pharmacological agents.