Advanced magnetic resonance imaging (MRI) approaches are extensively used for the assessment of central nervous system (CNS) damage in patients with multiple sclerosis (MS) and allied white matter diseases. Through their ability to obtain simultaneous measures of abnormalities of structure and function at a global and regional level, these techniques, which include magnetization transfer MRI, diffusion tensor MRI and proton MR spectroscopy, are contributing to filling the voids between clinical and MRI measures. As a consequence, they are dramatically improving our understanding of the mechanisms related to the accumulation of irreversible disability in these conditions. Future improvements, including the development of new sequences and post-processing methods as well as the use of high-field MRI, despite being a major technical challenge, hold new and exciting promise.