This chapter focuses on the treatment of acute disseminated encephalomyelitis (ADEM) in children. Early case series reported multiple regimens of corticosteroids for ADEM, including both oral and intravenous therapies, depending on the severity of neurologic impairment. A relapse may be associated with corticosteroid withdrawal or may signify an alternative diagnosis, such as recurrent ADEM, multiphasic disseminated encephalomyelitis, or multiple sclerosis (MS). Intravenous immunoglobulins (IVIg) have been used successfully as an alternative therapy for autoimmune diseases including ADEM. Plasma exchange, has been used to treat many neurologic diseases including Guillain-Barrésyndrome. The location of the lesions can cause a variety of neurologic deficits requiring additional treatment, such as anti-epileptic drugs for children with seizures and mechanical ventilation for brainstem or upper cervical cord involvement. The prognosis for children with ADEM is generally favorable. The clinical presentation and time to recovery are quite variable in children with ADEM.