Glutamate receptor ion channels mediate excitatory responses at the majority of CNS synapses. They are the only ligand-gated ion channels for which multiple high-resolution crystal structures have been solved. Highlights of information gained from mechanistic studies based on the crystal structures of their ligand-binding domains include explanations for strikingly diverse phenomena. These include the basis for subtype-specific agonist selectivity; mechanisms for desensitization and allosteric modulation; and mechanisms for partial agonist activity. In addition, multiple lines of evidence, including low-resolution electron microscopic studies, suggest that native AMPA receptors combine with an auxiliary subunit which regulates activity and trafficking. Functional studies suggest that glutamate receptor gating is distinct from that of structurally related voltage-gated ion channels.