The classical view of MS as an inflammatory-demyelinating condition affecting the white matter (WM) of the central nervous system (CNS) has recently been challenged by the results of several magnetic resonance imaging (MRI) studies. These consistently show grey matter (GM) involvement, which correlates only moderately with the extent of WM pathology. Here we summarize how conventional and modern imaging-based techniques have quantified GM damage in MS, in terms of focal lesions, diffuse tissue abnormalities and irreversible tissue loss. Results from functional MRI studies, together with these new findings, are contributing to a significant change in our MS understanding. MS is now viewed as a global CNS condition, affecting both WM and GM, which has an early and important neurodegenerative component.