Abstract | Although the core concept of remyelination — based on the activation, migration, proliferation and differentiation of CNS progenitors — has not changed over the past 20 years, our understanding of the detailed mechanisms that underlie this process has developed considerably. We can now decorate the central events of remyelination with a host of pathways, molecules, mediators and cells, revealing a complex and precisely orchestrated process. These advances have led to recent drug-based and cell-based clinical trials for myelin diseases, and have opened up hitherto unrecognized opportunities for drug-based approaches to therapeutically enhance remyelination.