Myelinating oligodendrocytes and oligodendrocyte precursor cells (OPCs) make up half the cells in the central nervous system and are affected by and contribute to all neurological diseases. The pathology of myelinating oligodendrocytes is fundamentally characterized by myelin disruption and loss, termed demyelination, whereas that of OPCs is principally defined by remyelination and repair in the form of regeneration of myelinating oligodendrocytes. Demyelination is generally associated with white matter diseases, such as multiple sclerosis, although oligodendroglial pathology is a major factor in most neuropathologies, including Alzheimer’s disease, ischaemic injury, and traumatic injury. Oligodendroglial changes are often driven by neuroinflammatory factors and involve oxidative stress, metabolic malfunction, and excitotoxicity. Understanding the complexities of demyelination and remyelination pathogenesis is essential for the development of new therapeutic strategies. In this chapter, we summarise the key features of demyelination and remyelination, discuss factors underlying a remyelination failure, and compare the differences between humans and mice. We propose some perspectives on treatment strategies for remyelination in the hope that future advances will provide solutions to the challenges associated with demyelinating diseases.