Acute disseminated encephalomyelitis (ADEM) is typically a monophasic, demyelinating disease of the CNS that predominantly affects children. Typically, its clinical symptoms follow an infection or vaccination. In this regard, numerous viral and bacterial pathogens as well as several vaccinations have been associated with ADEM. Studies from animal models suggest that primary and secondary autoimmune responses may contribute to CNS inflammation and demyelination in ADEM. The diagnosis of ADEM is strongly suggested by a close temporal relationship between a viral infection or immunization and the onset of neurologic symptoms, and it is supported by extensive, multifocal, subcortical white-matter disease on brain magnetic resonance imaging. While mild lymphocytic pleocytosis and elevated proteins are detectable in the CSF in ADEM, oligoclonal bands are not always present. Treatment of this disorder consists of anti-inflammatory and immunosuppressive therapies, and the prognosis is generally considered favorable.