This chapter discusses the characteristic MRI features of acute disseminated encephalomyelitis (ADEM), with particular emphasis on distinguishing it from the typical MRI of clinically isolated syndromes (CIS) and multiple sclerosis (MS). Typically spinal cord lesions in ADEM are large and extend over long segments of the spinal cord. The spinal lesions in ADEM are often edematous. The classical MRI of ADEM is of disseminated asymmetrical white matter lesions. Solitary tumor-like lesions are seen occasionally in ADEM. Bilateral basal ganglia involvement has been associated with a post-streptococcal variant of ADEM. Residual gliosis and demyelination occur in some ADEM patients. The differential diagnosis of ADEM is broad and requires a thorough clinical and investigation approach. The variable nature of ADEM imaging supports the hypothesis that ADEM is a heterogenous syndrome with different immunopathological mechanisms. Clinical, radiological, immunological and genetic studies clarify ADEM and associated disorders.