Disability in multiple sclerosis is related to demyelination and axonal injury. Remyelination has been shown to occur in the different forms of the disease. In addition to restoring nerve conduction, myelin repair has a major role in preventing neurodegeneration. However, although sometimes extensive, remyelination is usually insufficient. Our understanding of the cellular and molecular mechanisms underlying the success or failure of myelin repair has benefited from lesion analysis in multiple sclerosis, and from in vivo and in vitro models of myelination and remyelination. This also provides potential targets for therapeutic intervention aimed at promoting endogenous remyelination.