This review summarizes a general approach to pediatric demyelination as well as specific features of each of the acquired demyelinating syndromes to help clinicians in their evaluation of children with these disorders. Case studies are included to illustrate the expanding phenotype of many of these syndromes.With the creation of consensus definitions for the pediatric acquired demyelinating syndromes, recognition of demyelination in children has increased, as has understanding of the clinical and radiologic features, prognosis, and response to treatment. Collaborative studies and multicenter clinical trials are ongoing and needed to appropriately evaluate emerging therapies for some of the chronic demyelinating disorders, such as multiple sclerosis and neuromyelitis optica (NMO) spectrum disorder.This review will aid the clinician in identifying key features of the pediatric acquired demyelinating syndromes and highlights a general approach for the diagnosis and treatment of these disorders.