Acute disseminated encephalomyelitis is an idiopathic inflammatory demyelinating disease of the CNS that is particularly difficult to differentiate from the first episode of multiple sclerosis, so called clinically isolated syndrome. Currently, no diagnostic criteria exist that could reliably differentiate these two diseases. More importantly no single clinical, neuroimaging or cerebrospinal fluid feature defines a disorder with absolute certainty. This review will summarize clinical and paraclinical characteristics of acute disseminated encephalomyelitis in adults, with special emphasis on diagnostic imaging.