Acute demyelinating encephalomyelitis (ADEM) is increasingly recognized but difficult to define precisely: eleven papers have recently been published that used different definitions. Several diseases, most of them relapsing, can mimic ADEM at onset and require specific treatments. First, the distinction between early signs of multiple sclerosis and ADEM is controversial in the absence of specific biological characterization. To clarify it, epidemiological evaluations on large groups of children, of calculated risk factors for the occurrence of relapses after a first demyelinating event are probably the best approach. Macrophage activation syndrome and different types of angiitis may mimic ADEM, because they can occur in the absence of the usual non neurological symptoms. Both entities require specific treatments.