Remyelination is the process by which new myelin sheaths are restored to demyelinated axons and represents the best example of adult multipotent stem/precursor cells contributing to regeneration of the adult CNS. This process can occur with remarkable efficiency in both clinical disease such as multiple sclerosis, and in experimental models, revealing an impressive ability of the CNS to repair itself. However, remyelination often fails in diseases like multiple sclerosis, resulting in the disruption of signal conduction along the axon and eventually in axonal loss. Like other regenerative processes the efficiency of remyelination decreases with age and at a faster rate in males than in females. We have previously shown that this age-associated decline is due to an impairment of stem/precursor cell recruitment and, more significantly, their differentiation into remyelinating oligodendrocytes. These events correlate with age-associated changes in the inflammatory response to demyelination and in the expression profiles of several environmental signals such as growth factors involved in remyelination. The extent to which there are also intrinsic age-associated changes in the stem/precursor cells that mediate remyelination has not been fully explored but is likely to be a key factor. This talk will review this topic and indicate how understanding the effects of ageing on remyelination at the level of the systemic environment, the local signaling network and the remyelinating stem/precursor cell are crucial in order to devise means to enhance endogenous remyelination as a therapeutic approach to demyelinating disease.