In multiple sclerosis (MS) it is emerging that the most visible element of pathology, white matter (WM) lesions, represents only a fraction of the disease burden borne by the brain; non-lesional WM is also damaged, as is the grey matter (GM). Evidence is also accruing that GM damage may be a major determinant of longer-term outcomes in MS, and that such damage occurs from the earliest clinical stages of the disease. In this review, we focus on the early stages of relapse onset MS, considering the nature, extent and evolution of GM pathology, as determined using magnetic resonance imaging.