In several white matter diseases of the central nervous system (CNS), and in particular in multiple sclerosis, conventional magnetic resonance imaging (MRI) has proved to be sensitive for detecting lesions and their changes over time. However, conventional MRI is not able to characterize and quantify the tissue damage within and outside such lesions. Magnetization transfer MRI (MT-MRI) is a quantitative MRI 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. Metrics derived from MT-MRI can quantify the structural changes occurring within and outside lesions visible on conventional MRI scans. The present review summarizes the major contributions given by MT-MRI to provide an accurate in vivo picture of the heterogeneity of CNS pathology and, ultimately, to improve our ability to monitor the evolution of various neurological conditions.