The formation of the myelin sheath in the CNS is the endpoint of a defined developmental program along which oligodendrocytes progress. However, the molecular signals required for the initiation of myelination are largely unknown. Ishibashi et al. report in this issue of Neuron that ATP released by axons as a result of electrical stimulation serves as an important myelination signal. Surprisingly, they found that ATP does not act directly on oligodendrocytes but rather on astrocytes, causing the release of leukemia inhibitory factor (LIF), which in turns affects promyelinating oligodendrocytes. These findings uncover a novel role for astrocytes in mediating the intricate communication between axons and myelinating glial cells.