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This review will address the critical role of radiographic techniques in monitoring multiple sclerosis disease course and response to therapeutic interventions using conventional imaging. We propose an algorithm of obtaining a contrast-enhanced brain MRI 6 months after starting a disease-modifying therapy, and considering a gadolinium-enhancing lesion on that scan to indicate suboptimal response to therapy. New or enlarging T2 lesions should be followed on scans at 6-month intervals to assess for change, and the presence of one or more enhancing lesions on a 6- or 12-month scan, or two or more new or enlarging T2 lesions on a 12-month scan should prompt consideration of therapy change. New techniques such as PET imaging, magnetic resonance spectroscopy, magnetic resonance relaxometry, iron-sensitive imaging and perfusion MRI will also be overviewed, with their potential roles in monitoring disease course and activity.