Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system that is mediated by activated lymphocytes, macrophages/microglia, and complement. In MS, the myelin-forming oligodendrocytes (OLGs) are the targets of the immune attack. Experimental evidence indicates that C5b-9 plays a role in demyelination during the acute phase of experimental allergic encephalomyelitis (EAE). Terminal complement C5b-9 complexes are capable of protecting OLGs from apoptosis. During chronic EAE complement C5 promotes axonal preservation, remyelination and provides protection from gliosis. These findings indicate that the activation of complement and C5b-9 assembly can also have protective roles during demyelination.