Multiple sclerosis (MS) pathology is originally defined by the presence of focal white matter lesions, characterized by inflammation, primary demyelination, and reactive glial scaring. More recently, however, it became clear that focal white matter plaques in MS comprise of a broad spectrum of different lesion types, reflecting different stages of activity and different degrees of neurodegeneration or repair. In addition, the MS brain is affected by global changes in the normal-appearing white matter and gray matter. All types of changes in the MS brain and spinal cord occur on the background of inflammation; the type of inflammation, however, differs between different stages and forms of the disease.