This review discusses the use of experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS), highlighting its role in translational neuropharmacology. EAE is the most commonly used animal model for MS, a chronic inflammatory demyelinating disease of the central nervous system (CNS). It mimics key pathological features of MS, including inflammation, demyelination, axonal loss, and gliosis. EAE also models immune-mediated neuroinflammation and neurodegeneration, and has been used to develop and test many drugs currently used in MS treatment. EAE is a complex model with significant variability in susceptibility, induction methods, and response to immunological or neuropharmacological interventions. This variability makes EAE a versatile system for studying immune and neural mechanisms of MS, but it also presents challenges in translating findings to human disease. Despite these challenges, EAE has been instrumental in developing therapies for MS, including interferons, glatiramer acetate, and natalizumab. However, some treatments that work in EAE have not translated successfully to MS, highlighting the need for careful model selection and validation. EAE has also been used to study other autoimmune diseases and to explore new therapeutic approaches, such as altered peptide ligands and adhesion molecule blockade. While some treatments have shown promise in EAE, their efficacy in MS remains uncertain. The review emphasizes the importance of using appropriate animal models to guide clinical drug development and highlights the need for further research to improve the translation of findings from EAE to human MS.This review discusses the use of experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS), highlighting its role in translational neuropharmacology. EAE is the most commonly used animal model for MS, a chronic inflammatory demyelinating disease of the central nervous system (CNS). It mimics key pathological features of MS, including inflammation, demyelination, axonal loss, and gliosis. EAE also models immune-mediated neuroinflammation and neurodegeneration, and has been used to develop and test many drugs currently used in MS treatment. EAE is a complex model with significant variability in susceptibility, induction methods, and response to immunological or neuropharmacological interventions. This variability makes EAE a versatile system for studying immune and neural mechanisms of MS, but it also presents challenges in translating findings to human disease. Despite these challenges, EAE has been instrumental in developing therapies for MS, including interferons, glatiramer acetate, and natalizumab. However, some treatments that work in EAE have not translated successfully to MS, highlighting the need for careful model selection and validation. EAE has also been used to study other autoimmune diseases and to explore new therapeutic approaches, such as altered peptide ligands and adhesion molecule blockade. While some treatments have shown promise in EAE, their efficacy in MS remains uncertain. The review emphasizes the importance of using appropriate animal models to guide clinical drug development and highlights the need for further research to improve the translation of findings from EAE to human MS.