Apart from its great diagnostic impact, conventional MR imaging provides only limited insights into the pathophysiologic changes of multiple sclerosis (MS). This fact is most easily seen from the relatively poor correlation between the extent of MR signal abnormalities and clinical disability in established MS. Diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) have the potential to improve on the detection and characterization of MS-associated tissue changes. This potential will contribute to an increase in understanding of disease conditions that seem to coexist with MS and may be useful as an additional method for monitoring specific mechanisms of disease progression. Moreover, DWI and DTI may play a complimentary role in the assessment of other white-matter diseases with MR imaging in a similar manner.