Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system. Available treatments (immuno-modulators, immuno-suppressants) limit central nervous system inflammation and are only partially effective. Remyelination of naked axons becomes insufficient in most cases as the disease progresses. The reason for this repair deficit are many, including oligodendroglial, axonal and environmental factors. Understanding why remyelination fails is crucial for devising effective methods by which to enhance it.