In this article we discuss the molecular signaling mechanisms that coordinate interactions between Schwann cells and the neurons of the peripheral nervous system. Such interactions take place perpetually during development and in adulthood, and are critical for the homeostasis of the peripheral nervous system (PNS). Neurons provide essential signals to control Schwann cell functions, whereas Schwann cells promote neuronal survival and allow efficient transduction of action potentials. Deregulation of neuron–Schwann cell interactions often results in developmental abnormalities and diseases. Recent investigations (...) have shown that during development, neuronally provided signals, such as Neuregulin, Jagged, and Wnt interact to fine‐tune the Schwann cell lineage progression. In adult, the signal exchange between neurons and Schwann cells ensures proper nerve function and regeneration. Identification of the mechanisms of neuron–Schwann cell interactions is therefore essential for our understanding of the development, function and pathology of the peripheral nervous system as a whole. -/- . (shrink)