Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) affecting over 2 million people worldwide, with a significant economic impact. The disease is characterized by episodes of neurological disability that can be reversible or lead to progressive impairment over time. Modern techniques like MRI and immunohistochemistry have revolutionized our understanding of MS pathology, revealing that lesions can appear in various CNS regions, including white and gray matter, brainstem, spinal cord, and optic nerve. Early stages of white matter demyelination are heterogeneous and evolve over months, with a single immune-effector mechanism dominating in each individual. The long-term fate of lesions—whether they resolve, remit, or progress—remains poorly understood, but recent data suggest that younger individuals may have more effective lesion repair. Cortical lesions, often perivascular, are less inflammatory and have less blood-brain-barrier permeability. Spinal cord lesions and atrophy are major sources of clinical disability, while retinal damage, detectable by optical coherence tomography, can predict disability evolution. Genetic and environmental factors contribute to MS risk, with genetic risk factors being more significant. Therapeutic approaches aim to modify the course of MS, with current treatments reducing the frequency of relapses and new lesion formation but not fully preventing progressive disability. Ocrelizumab, a B-cell targeting therapy, has shown promise in primary progressive MS. Future research should focus on lesion development and repair, unifying lines of research and improving biomarker development for early intervention.Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) affecting over 2 million people worldwide, with a significant economic impact. The disease is characterized by episodes of neurological disability that can be reversible or lead to progressive impairment over time. Modern techniques like MRI and immunohistochemistry have revolutionized our understanding of MS pathology, revealing that lesions can appear in various CNS regions, including white and gray matter, brainstem, spinal cord, and optic nerve. Early stages of white matter demyelination are heterogeneous and evolve over months, with a single immune-effector mechanism dominating in each individual. The long-term fate of lesions—whether they resolve, remit, or progress—remains poorly understood, but recent data suggest that younger individuals may have more effective lesion repair. Cortical lesions, often perivascular, are less inflammatory and have less blood-brain-barrier permeability. Spinal cord lesions and atrophy are major sources of clinical disability, while retinal damage, detectable by optical coherence tomography, can predict disability evolution. Genetic and environmental factors contribute to MS risk, with genetic risk factors being more significant. Therapeutic approaches aim to modify the course of MS, with current treatments reducing the frequency of relapses and new lesion formation but not fully preventing progressive disability. Ocrelizumab, a B-cell targeting therapy, has shown promise in primary progressive MS. Future research should focus on lesion development and repair, unifying lines of research and improving biomarker development for early intervention.