Baló's concentric sclerosis (BCS) has long been considered to be a variant of multiple sclerosis. Although BCS was initially described over 100 years ago, relatively few antemortem cases have been identified, and the exact pathogenesis remains unknown. Inflammatory protective ischemic preconditioning has recently been suggested as a mechanism by which the typical concentric rings of the BCS lesion are formed. Advanced neuroimaging can provide important in vivo markers of disease progression that can assist in the diagnosis and management of patients with BCS. In this Review, we discuss evidence from longitudinal neuroimaging studies that supports the role of ischemic preconditioning in BCS.