Multiple sclerosis (MS) is considered the most common inflammatory autoimmune neurologic disorder and the most frequent cause of nontraumatic neurologic disability in young and middle-age adults. This article reviews the basic features of its magnetic resonance (MR) imaging lesions and, primarily, the use of diffusion MR imaging, which is increasingly applied to assess patients with MS, not only to investigate plaques but also the normal-appearing white matter, gray matter, optic nerve, and spinal cord, because of its ability to detect and quantify disease-related pathologic conditions of the central nervous system.