Multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM) are conditions whose closely related pathology suggests shared pathophysiological elements, but whose clinical courses are usually, but not always quite dissimilar. The former is largely a disease of adulthood, the latter of childhood. Optic neuritis, demyelinative transverse myelitis, and Devic's syndrome are neurological syndromes that may occur as manifestations of either MS or ADEM. Patients with Miller-Fisher syndrome and encephalomyelradiculoneuropathy usually have features suggesting ADEM in combination with acute demyelinative polyneuropathy. These various conditions and other forms of ADEM share an indistinct border with encephalitides, granulomatous, and vasculitic conditions. MS, ADEM, and the pertinent syndromic subtypes, their differential diagnosis, treatment, and prognosis are considered in this review. Acute cerebellar ataxia is a syndrome that is likely to be pathophysiologically distinct from ADEM, although its occurrence as a postinfectious illness suggests a distant kinship. It is also reviewed.