The myelin membrane wrapped around axons provides electrical insulation essential for rapid impulse conduction. Impulse activity can affect the formation of myelin, but the effects differ in the PNS and CNS, where myelin is formed by two distinct types of cells: Schwann cells (SCs) and oligodendrocytes, respectively. Our studies on mouse dorsal root ganglion (DRG) neurons, which have axons in both the PNS and CNS, show that impulse activity releases ATP from premyelinated axons, and that this is detected by myelinating glia. Calcium imaging indicates that axonal firing stimulates different purinergic receptors on the two types of glia, resulting in opposite effects of impulse activity on differentiation of SCs and oligodendrocyte progenitor cells (OPCs). In addition to P2 receptors on both types of glia, four types of P1 receptors are present in OPCs, but only A2A and A2BP1 receptors are detected in mouse SCs. ATP is of primary importance in regulating early development and myelination by SCs, where it inhibits differentiation and myelination. Adenosine is of primary importance in regulating early development of OPCs, where it stimulates differentiation and myelination. Purinergic signalling interacts with growth factor and cytokine signalling, and these responses are developmentally regulated.