The myelination of the axons of the central nervous system (CNS) is assumed by the oligodendrocytes, which depend at least in part on signals of axonal origin. The axonal influence on myelination seems to consist of the sum of positive and negative factors, which can either act on the axon or on the oligodendrocyte, allowing the neuron to decide when and where myelinization is initiated. The induction factors appear to be mediated, in some cases, by electrical activity. Among the negative factors, certain factors such as the adhesion molecule PSA-NCAM seem to act by inhibiting the adhesion between the axon and the oligodendrocytic extension. Others, such as the inhibitory signalling pathway, jagged1/Notch1, appear to trigger an inhibitory oligodendroglial signalling, therapy preventing maturation and myelination. The recent determination of the role of these axonal signals has provided a new approach to the mechanisms of normal myelination. These results could be extrapolated to the process of remyelination in human demyelinating pathologies such as multiple sclerosis, and open up new therapeutic research possibilities aimed at neuronal protection.