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This review summarizes the recent data pertaining to the use of magnetic resonance imaging (MRI) in assessing brain and spinal cord involvement in multiple sclerosis (MS).Using MRI as a tool, investigators have made progress recently in understanding the substrate and mechanisms underlying the development and evolution of focal lesions and diffuse damage in MS. The application of refined MRI sequences has markedly improved the characterization of focal lesions, in particular cortical lesions. Promising improvements have been made to clarify the pathological specificity and sensitivity of MRI techniques by performing combined histopathologic–MRI correlation studies. The use of high-field (3 T) and ultra-high-field (UHF; >3 T) MRI has further facilitated the detection of both gray matter and white matter microstructural damage, and elucidated the topographic relationship of overt damage to venous blood vessels. The development of advanced MRI postprocessing tools has led to additional progress in detecting clinically relevant regional gray matter and white matter damage.MRI continues to play a pivotal role in the investigation of MS. Ongoing advances in MRI technology should further expand the current understanding of pathologic disease mechanisms and improve diagnostic, prognostic, and monitoring ability in patients with MS.