Magnetic resonance (MR) imaging is very sensitive in showing disseminated MS lesions. Subclinical MR progression occurs frequently, explaining why MR is now used to monitor treatment, even without measurable consequences, of new MR lesions to the patient at this moment. In the light of this clinico-radiological paradox, the significance of MR in MS is discussed, particularly in relation with the expanded disability status scale (EDSS). Gadolinium-enhancing lesions correlate with the occurrence of relapses, CSF myelin breakdown products and, in patients with relapsing-remitting disease, with higher EDSS. However, the predictive value of the frequency of enhancement for changes in EDSS is only weak. For conventional T2-weighted MR imaging, the cross-sectional correlation with EDSS varies between 0.15 and 0.60, and is limited mainly by the inherent lack of tissues specificity of T2-weighted images. Both T1 black holes and magnetisation transfer (MT) parameters show a better correlation with EDSS; it should be noted that lesions in which those abnormalities are found go through an initial phase of enhancement as well. For T1 black holes, a correlation up to 0.81 has been reported for SP patients. Post-mortem studies show that black holes and low MT ratios are in vivo markers of axonal loss. Preliminary data indicate that progressive atrophy also correlates with progression on the EDSS scale. More should be learned about the fate of new MR lesion with regards to development of axonal loss, which at present is difficult to predict in the enhancing stage. The existence of escape mechanisms, including remyelination, make a simple correlation with EDSS extremely unlikely, and perhaps not even desirable. Nevertheless, while the clinical effect of a given new lesion may be difficult to ascertain, the absence of (new) MR lesions is prognostically favourable, as will be the degree to which new lesions are prevented by treatment.