Deficits in memory and attention frequently occur during the course of multiple sclerosis (MS). In patients with MS the severity of cognitive manifestations is not closely related to indices of structural brain damage on both conventional and non conventional magnetic resonance imaging (MRI). It is conceivable that the ability of the brain to compensate for tissue impairment or loss may contribute to the maintenance of normal performance despite scattered brain lesions. Accordingly, using functional MRI (fMRI), patients with multiple sclerosis showed a greater extent of brain activation during motors tasks than controls. Changes in functional organization of the cerebral cortex have also been reported by fMRI studies comparing the activation patterns during cognitive tasks in patients with MS and in healthy subjects. Differences in patients' selection, activation paradigm, experimental design and MR acquisition parameters make, however, the results obtained from fMRI studies difficult to be compared and may explain, at least partially, some discrepant findings. Nevertheless, fMRI studies provide a new interesting way of understanding how the brain can change its functional organization in response to MS pathology, and might be useful in the study of the effects of either rehabilitation or pharmacological agents on brain plasticity.