In multiple sclerosis (MS), conventional magnetic resonance imaging (MRI) has proved to be sensitive for detecting lesions and their changes over time. However, conventional MRI cannot characterize and quantify the tissue damage within and outside such lesions. Other quantitative MR techniques, including MR spectroscopy (MRS), magnetization transfer imaging (MTI) and diffusion-weighted imaging (DWI) have the potential to overcome this limitation and, as a consequence, to provide complementary information to conventional MRI. MTI- and DWI-derived measurements quantify the structural changes occurring within and outside lesions seen on conventional MRI scans, and MRS adds information on the biochemical nature of such changes. The application of these MR techniques to the study of MS is dramatically increasing our understanding of how MS causes irreversible deficits, and it is likely to provide useful insights into the pathophysiology of other white matter diseases in the future. The present review summarizes the major contributions made by these three MR techniques in the understanding of MS evolution.