AbstractRecent years have witnessed impressive advances in the use of magnetic resonance imaging (MRI) for the assessment of patients with multiple sclerosis (MS). Complementary to the clinical evaluation, conventional MRI provides crucial pieces of information for the diagnosis of MS. However, the correlation between the burden of lesions observed on conventional MRI scans and the clinical manifestations of the disease remains weak. The discrepancy between clinical and conventional MRI findings in MS is explained, at least partially, by the limited ability of conventional MRI to characterize and quantify the heterogeneous features of MS pathology. Other quantitative MR‐based techniques, however, have the potential to overcome such a limitation of conventional MRI. Indeed, magnetization transfer MRI, diffusion tensor MRI, proton MR spectroscopy, and functional MRI are contributing to elucidate the mechanisms that underlie injury, repair, and functional adaptation in patients with MS. Such techniques are likely to benefit from the use of high‐field MR systems and thus allow in the near future providing additional insight into all these aspects of the disease. This review summarizes how MRI is dramatically changing our understanding of the factors associated with the accumulation of irreversible disability in MS and highlights the reasons why they should be used more extensively in studies of disease evolution and clinical trials. J. Magn. Reson. Imaging 2010;31:770–788. ©2010 Wiley‐Liss, Inc.