BACKGROUND: MRI has revolutionized the diagnostic accuracy of multiple sclerosis (MS) in adults, and is now used extensively to evaluate efficacy of immunomodulatory therapies. Although MRI has also been used to aid in the diagnosis and care of children with MS, the MRI features of MS in children are less well understood. METHODS: The present review summarizes the available literature on MRI in pediatric MS, outlines the specific features of other disorders affecting the CNS white matter in children, compares the MRI appearance of MS in children to seminal neuroimaging studies in adult-onset MS, and discusses the potential role of advanced MRI technologies in delineating the underlying pathobiology of acquired demyelinating disease in children. RESULTS: Although the MRI features of MS in children have similarity to adult-onset MS, children tend to have fewer lesions and a lower propensity for lesions to enhance with gadolinium. The MRI findings in children presenting with a clinical phenotype of acute disseminated encephalomyelitis may be indistinguishable from the first attack of MS. CONCLUSIONS: MRI criteria specific for pediatric-onset multiple sclerosis (MS) and criteria predictive of MS outcome in children experiencing a first demyelinating event will be challenged by the overlap in MRI features between acute monophasic demyelinating syndromes and MS, particularly in younger children. Emergence of new clinically silent lesions on MRI scans separated by at least 3 months is characteristic of MS. Newer MRI techniques evaluating white matter biochemistry and integrity in the youngest MS patients may provide new insights into the relative contributions of inflammation and neurodegeneration in MS. ©2007AAN Enterprises, Inc.