In multiple sclerosis (MS), conventional magnetic resonance imaging (cMRI) has proved to be sensitive for detecting lesions and their changes over time. However, cMRI is not able to characterize and quantify the tissue damage within and outside such lesions. Magnetization transfer (MT) MRI is a quantitative technique with the potential to overcome this limitation and, as a consequence, to provide additional information about the nature and the extent of tissue damage associated to this disease. During the last 10 years, MT MRI indeed has allowed us to quantify the structural changes occurring within and outside lesions visible on cMRI scans, thus providing a more accurate in vivo picture of the heterogeneity of MS and, as a consequence, improving our ability to monitor the evolution of the disease. The application of MT MRI to the study of MS has contributed to change our understanding of how MS causes irreversible disability by showing that MS is more than an inflammatory-demyelinating condition of the white matter of the central nervous system.