Magnetic resonance imaging plays an essential role in the diagnosis and management of pediatric central nervous system (CNS) autoimmune disorders. This article reviews the key clinical and conventional neuroimaging characteristics of the most frequent entities of the demyelinating disease spectrum, with a goal to inform and guide decisions in the clinical practice. We focus on acquired demyelinating syndromes and their differential diagnoses including mimics such as systemic inflammatory disorders with secondary CNS involvement. In the vast majority of disorders, no specific biomarker of disease is known and the final diagnosis is based on recognizable syndromic characteristics. Therefore, familiarity with the related neuroimaging patterns can improve a timely diagnosis of pediatric autoimmune diseases and prompt targeted therapeutic approach.