Excitotoxicity, caused by excessive activation of glutamate receptors, plays a critical role in neurodegenerative diseases. This review discusses the molecular mechanisms of excitotoxicity and its relevance to the pathogenesis of neurodegenerative disorders. Excessive glutamate leads to calcium overload, free radical generation, and mitochondrial dysfunction, contributing to neuronal death. Excitotoxicity is implicated in various neurodegenerative conditions, suggesting a common pathogenic pathway despite diverse genetic causes. Understanding these mechanisms is crucial for developing therapeutic strategies. Excitotoxicity involves both ionotropic (NMDA, AMPA, KA) and metabotropic (mGluR) glutamate receptors. NMDA receptors are particularly involved in calcium influx and subsequent neuronal damage. AMPA receptors, when permeable to calcium, contribute to delayed neuronal death. Metabotropic receptors, such as mGluR2, may protect neurons by reducing oxidative stress. Excess glutamate and glutamatergic activity are observed in neurodegenerative diseases, leading to excitotoxicity. Excitotoxicity is mediated by ion transport, including Na⁺, Cl⁻, and Ca²⁺. Excessive Ca²⁺ influx through glutamate receptors leads to mitochondrial dysfunction and apoptosis. Oxidative stress, caused by free radicals, exacerbates neuronal damage by damaging proteins, lipids, and DNA. Nitric oxide (NO) and its metabolite ONOO⁻ contribute to oxidative stress and neurotoxicity in neurodegenerative diseases. Mitochondria play a central role in excitotoxicity, as their dysfunction leads to calcium overload, ROS production, and apoptosis. Mitochondrial permeability transition and the release of proapoptotic factors contribute to cell death. Autophagy and apoptosis are also involved in excitotoxic neuronal injury. Excitotoxicity is implicated in various neurodegenerative diseases, including Huntington's, Alzheimer's, and Parkinson's. In Huntington's disease, mutant huntingtin protein disrupts NMDA receptor function and calcium signaling. In Alzheimer's, Aβ accumulation and glutamatergic dysfunction contribute to excitotoxicity. In Parkinson's, mitochondrial dysfunction and oxidative stress are key factors. Understanding the molecular pathways of excitotoxicity is essential for developing targeted therapies. This review highlights the complex interplay between excitotoxicity, oxidative stress, and mitochondrial dysfunction in neurodegenerative diseases, emphasizing the need for further research to identify effective therapeutic strategies.Excitotoxicity, caused by excessive activation of glutamate receptors, plays a critical role in neurodegenerative diseases. This review discusses the molecular mechanisms of excitotoxicity and its relevance to the pathogenesis of neurodegenerative disorders. Excessive glutamate leads to calcium overload, free radical generation, and mitochondrial dysfunction, contributing to neuronal death. Excitotoxicity is implicated in various neurodegenerative conditions, suggesting a common pathogenic pathway despite diverse genetic causes. Understanding these mechanisms is crucial for developing therapeutic strategies. Excitotoxicity involves both ionotropic (NMDA, AMPA, KA) and metabotropic (mGluR) glutamate receptors. NMDA receptors are particularly involved in calcium influx and subsequent neuronal damage. AMPA receptors, when permeable to calcium, contribute to delayed neuronal death. Metabotropic receptors, such as mGluR2, may protect neurons by reducing oxidative stress. Excess glutamate and glutamatergic activity are observed in neurodegenerative diseases, leading to excitotoxicity. Excitotoxicity is mediated by ion transport, including Na⁺, Cl⁻, and Ca²⁺. Excessive Ca²⁺ influx through glutamate receptors leads to mitochondrial dysfunction and apoptosis. Oxidative stress, caused by free radicals, exacerbates neuronal damage by damaging proteins, lipids, and DNA. Nitric oxide (NO) and its metabolite ONOO⁻ contribute to oxidative stress and neurotoxicity in neurodegenerative diseases. Mitochondria play a central role in excitotoxicity, as their dysfunction leads to calcium overload, ROS production, and apoptosis. Mitochondrial permeability transition and the release of proapoptotic factors contribute to cell death. Autophagy and apoptosis are also involved in excitotoxic neuronal injury. Excitotoxicity is implicated in various neurodegenerative diseases, including Huntington's, Alzheimer's, and Parkinson's. In Huntington's disease, mutant huntingtin protein disrupts NMDA receptor function and calcium signaling. In Alzheimer's, Aβ accumulation and glutamatergic dysfunction contribute to excitotoxicity. In Parkinson's, mitochondrial dysfunction and oxidative stress are key factors. Understanding the molecular pathways of excitotoxicity is essential for developing targeted therapies. This review highlights the complex interplay between excitotoxicity, oxidative stress, and mitochondrial dysfunction in neurodegenerative diseases, emphasizing the need for further research to identify effective therapeutic strategies.