Multiple sclerosis (MS) is considered a prototypical inflammatory autoimmune disease of the central nervous system that affects both myelin and axon. One of the most challenging aspects of MS is understanding the nature and mechanism of tissue injury because inflammation, demyelination, axonal degeneration, microvascular injury, and atrophy are all identified in histopathologic studies. Magnetic resonance (MR) imaging provides an in vivo examination of the brain that directly defines the extent of the pathology. In recent years, extensive MR studies have had a major impact on MS not only in making an early diagnosis but also in understanding of the disease. By exploiting the natural history and histopathologic correlation, conventional and various novel quantitative MR techniques have demonstrated the ability to image underlying pathological processes in MS. This review examines the role of different MR techniques in going beyond anatomical imaging and produces a more comprehensive overview of the pathophysiological changes which occur and evolve in MS.