The development of myelinated axons represents one of the most complex interactions among different cell types in the nervous system. Striking changes occur in both morphology and function in the early postnatal period. Myelination effectively isolates electrically most of the axolemma and dramatically alters the pathways for current flow that are required for rapid, reliable, and efficient conduction. Correspondingly, ion channels must be directed to and stabilized at their required sites. In the case of Na+ channels, this requires a 25-fold increase in density within nodes of Ranvier, and, in mammalian fibers, a virtually complete spatial separation from voltage-dependent K+ channels. Nodes must also be properly spaced to ensure a high conduction velocity and energy efficiency without compromising the safety factor for reliable propagation. In this review, we consider the events responsible for axon development, emphasizing the involvement of ion channels. We discuss the current state of research in this area, including some controversies regarding mechanisms of neuron-glial communication.