NMDA receptors (NMDARs) are glutamate-gated ion channels that play crucial roles in excitatory synaptic transmission and are implicated in various neurological disorders. NMDARs consist of multiple subtypes, differing in their subunit composition and pharmacological properties. The review discusses the molecular organization and functional domains of NMDAR subunits, including the N-terminal domain (NTD), agonist-binding domain (ABD), and ion-channel pore. Recent structural and functional data have revealed the molecular determinants for subunit-selective modulation, such as binding sites for glutamate, the ABD, and the NTD. The review also highlights the potential of NTDs as therapeutic targets, with ifenprodil and zinc identified as highly selective modulators of NR2B and NR2A-containing receptors, respectively. Additionally, the review explores the pharmacology of NMDAR subtypes, including competitive antagonists, channel blockers, and allosteric modulators. The therapeutic potential of NMDARs is discussed, particularly in the context of conditions like excitotoxicity, neurodegenerative disorders, and cognitive impairments. The review concludes by emphasizing the importance of understanding the subunit-specific properties of NMDARs for developing more selective and effective therapeutic agents.NMDA receptors (NMDARs) are glutamate-gated ion channels that play crucial roles in excitatory synaptic transmission and are implicated in various neurological disorders. NMDARs consist of multiple subtypes, differing in their subunit composition and pharmacological properties. The review discusses the molecular organization and functional domains of NMDAR subunits, including the N-terminal domain (NTD), agonist-binding domain (ABD), and ion-channel pore. Recent structural and functional data have revealed the molecular determinants for subunit-selective modulation, such as binding sites for glutamate, the ABD, and the NTD. The review also highlights the potential of NTDs as therapeutic targets, with ifenprodil and zinc identified as highly selective modulators of NR2B and NR2A-containing receptors, respectively. Additionally, the review explores the pharmacology of NMDAR subtypes, including competitive antagonists, channel blockers, and allosteric modulators. The therapeutic potential of NMDARs is discussed, particularly in the context of conditions like excitotoxicity, neurodegenerative disorders, and cognitive impairments. The review concludes by emphasizing the importance of understanding the subunit-specific properties of NMDARs for developing more selective and effective therapeutic agents.