This selective review of Schwann cell biology focuses on questions relating to the origins, development and differentiation of Schwann cells and the signals that control these processes. The importance of neuregulins and their receptors in controlling Schwann cell precursor survival and generation of Schwann cells, and the role of these molecules in Schwann cell biology is addressed. The reciprocal signalling between peripheral glial cells and neurons in development and adult life revealed in recent years is highlighted, and the profound change in survival regulation from neuron-dependent Schwann cell precursors to adult Schwann cells that depend on autocrine survival signals is discussed. Besides providing neuronal and autocrine signals, Schwann cells signal to mesenchymal cells and influence the development of the connective tissue sheaths of peripheral nerves. The importance of Desert Hedgehog in this process is described. The control of gene expression during Schwann cell development and differentiation by transcription factors is reviewed. Knockout of Oct-6 and Krox-20 leads to delay or absence of myelination, and these results are related to morphological or physiological observations on knockout or mutation of myelin-related genes. Finally, the relationship between selected extracellular matrix components, integrins and the cytoskeleton is explored and related to disease.