Mitochondria play essential roles in neurons and abnormal functions of mitochondria have been implicated in neurological disorders including myelin diseases. Since mitochondrial functions are regulated and maintained by their dynamic behavior involving localization, transport, and fusion/fission, modulation of mitochondrial dynamics would be involved in physiology and pathology of myelinated axons. In fact, the integration of multimodal imaging in vivo and in vitro revealed that mitochondrial localization and transport are differentially regulated in nodal and internodal regions in response to the changes of metabolic demand in myelinated axons. In addition, the mitochondrial behavior in axons is modulated as adaptive responses to demyelination irrespective of the cause of myelin loss, and the behavioral modulation is partly through interactions with cytoskeletons and closely associated with the pathophysiology of demyelinating diseases. Furthermore, the behavior and functions of axonal mitochondria are modulated in congenital myelin disorders involving impaired interactions between axons and myelin-forming cells, and, together with the inflammatory environment, implicated in axonal degeneration and disease phenotypes. Further studies on the regulatory mechanisms of the mitochondrial dynamics in myelinated axons would provide deeper insights into axo-glial interactions mediated through myelin ensheathment, and effective manipulations of the dynamics may lead to novel therapeutic strategies protecting axonal and neuronal functions and survival in primary diseases of myelin.