MRI is now an important component in the diagnosis and assessment of multiple sclerosis (MS). Evidence gleaned from imaging studies has changed our understanding of the pathophysiology and natural history of the disease and has enabled physicians to visualize the effects of immunomodulatory therapies. Serial MRI following the index CNS event has clarified the evolution of MS, demonstrating that a majority of patients with clinically isolated syndromes already have dissemination of lesions in space and, based on MRI characteristics, likely also in time. Imaging studies have also shown that axonal injury and brain atrophy occur early in the disease. MRI techniques, such as magnetic resonance spectroscopy and magnetization transfer imaging, that are generally not part of the imaging sequences obtained as part of regular care have provided additional insight into the degree and extent of the effect of the disease process on the CNS, tissue repair, and the neuroprotective effects of therapeutics. These data have contributed to improved clinical decision making and treatment outcomes.