The mammalian ionotropic glutamate receptor family consists of 18 gene products that assemble to form ligand-gated ion channels. These receptors mediate fast excitatory synaptic transmission in the central nervous system and are found on both neuronal and non-neuronal cells. They play crucial roles in various neurological processes and diseases. The structure of glutamate receptors, including their transmembrane elements, reveals a complex assembly of multiple semiautonomous extracellular domains linked to a pore-forming element with similarities to an inverted potassium channel. This review covers the nomenclature, structure, assembly, accessory subunits, interacting proteins, gene expression and translation, post-translational modifications, agonist and antagonist pharmacology, allosteric modulation, mechanisms of gating and permeation, roles in normal physiological function, and potential therapeutic uses. The structure of glutamate receptors has been elucidated through electron microscopy and crystallography, revealing a 2-fold rotational symmetry and a 4-fold symmetry in the ion channel domain. The subunits form distinct types of contacts, such as A/B and C/D subunits, and exhibit sequence homology and conserved residues. Assembly occurs in the endoplasmic reticulum, with initial dimer formation mediated by the amino-terminal domain (ATD) and subsequent tetramerization through interactions of the ligand-binding domain (LBD) and transmembrane domain (TMD). The LBD is highly conserved and adopts a clamshell-like conformation, with the agonist binding pocket located between two lobes. The ATD plays a crucial role in receptor oligomerization and trafficking, and may also bind endogenous ligands and regulatory proteins. The TMD consists of three transmembrane helices and a membrane-reentrant loop, with sequence homology to the inverted ion channel domain of potassium channels. The permeation properties of AMPA and kainate receptors can be modified post-transcriptionally by RNA editing at the Gln codon.The mammalian ionotropic glutamate receptor family consists of 18 gene products that assemble to form ligand-gated ion channels. These receptors mediate fast excitatory synaptic transmission in the central nervous system and are found on both neuronal and non-neuronal cells. They play crucial roles in various neurological processes and diseases. The structure of glutamate receptors, including their transmembrane elements, reveals a complex assembly of multiple semiautonomous extracellular domains linked to a pore-forming element with similarities to an inverted potassium channel. This review covers the nomenclature, structure, assembly, accessory subunits, interacting proteins, gene expression and translation, post-translational modifications, agonist and antagonist pharmacology, allosteric modulation, mechanisms of gating and permeation, roles in normal physiological function, and potential therapeutic uses. The structure of glutamate receptors has been elucidated through electron microscopy and crystallography, revealing a 2-fold rotational symmetry and a 4-fold symmetry in the ion channel domain. The subunits form distinct types of contacts, such as A/B and C/D subunits, and exhibit sequence homology and conserved residues. Assembly occurs in the endoplasmic reticulum, with initial dimer formation mediated by the amino-terminal domain (ATD) and subsequent tetramerization through interactions of the ligand-binding domain (LBD) and transmembrane domain (TMD). The LBD is highly conserved and adopts a clamshell-like conformation, with the agonist binding pocket located between two lobes. The ATD plays a crucial role in receptor oligomerization and trafficking, and may also bind endogenous ligands and regulatory proteins. The TMD consists of three transmembrane helices and a membrane-reentrant loop, with sequence homology to the inverted ion channel domain of potassium channels. The permeation properties of AMPA and kainate receptors can be modified post-transcriptionally by RNA editing at the Gln codon.