Remyelination by oligodendrocytes occurs early in the MS lesion, as documented by myelin sheaths that are abnormally thin relative to axon diameter. These thin myelin sheaths are often seen prominently at the edge of demyelinated plaques. A recent series of studies has shown that within weeks of the initial event, there is extensive oligodendrocyte regeneration and remyelination. These immature oligodendrocytes express a series of developmentally restricted antigens. This finding has been interpreted to suggest that the cells that repopulate the acute plaque and that affect remyelination are newly generated and not residual, mature oligodendrocytes. These observations support the possibility that factors that promote remyelination could be used to improve clinical recovery in ON and MS.