Multiple sclerosis (MS) is considered to be an autoimmune, inflammatory disease of the CNS. In most patients, the disease follows a relapsing - remitting course and is characterized by dynamic inflammatory demyelinating lesions in the CNS. Although on the surface MS may appear consistent with a primary autoimmune disease, questions have been raised as to whether inflammation and/or autoimmunity are really at the root of the disease, and it has been proposed that MS might in fact be a degenerative disorder. We argue that MS may be an 'immunological convolution' between an underlying primary degenerative disorder and the host's aberrant immune response. To better understand this disease, we might need to consider non-inflammatory primary progressive MS as the 'real' MS, with inflammatory forms reflecting secondary, albeit very important, reactions. © 2012 Macmillan Publishers Limited. All rights reserved.