Inflammatory demyelinating diseases comprise a spectrum of disorders that affect central nervous system (CNS) and peripheral nervous system (PNS) myelin. Most individuals have demyelinating disease restricted to one or the other compartment but patients with concomitant CNS and PNS inflammatory inflammatory demyelinating processes have been reported not infrequently. In most such patients, involvement of either the CNS or the PNS predominates the clinical picture. Involvement of the other compartment is usually mild or subclinical with unclear prognostic and therapeutic implications. Similarly, while experimentally induced demyelinating disease in animal models is usually CNS or PNS predominant, varying degrees of pathology in the other system can occur depending on the species, type of immunogen, and genetic background of the immunized animal. When CNS and PNS demyelinating diseases occur concurrently, effective treatment for CNS disease can be safely combined with effective treatment for PNS disease.