The extracellular matrix (ECM) occupies a notable proportion of the CNS and contributes to its normal physiology. Alterations to the ECM occur after neural injury (for example, in multiple sclerosis, spinal cord injury or Alzheimer's disease) and can have drastic consequences. Of note, injury-induced changes in chondroitin sulphate proteoglycans (CSPGs) — a family of ECM proteoglycans — can lead to the inhibition of myelin repair. Here, we highlight the pathophysiological roles of the brain's ECM, particularly those of CSPGs, after neural insults and discuss how the ECM can be targeted to promote remyelination.