Neuregulin 1 (Nrg1) and ErbB receptor tyrosine kinase signalling is essential for the formation and proper functioning of multiple organ systems and inappropriate Nrgl/ErbB signalling severely compromises health, contributing to such diverse pathologies as cancer and neuropsychiatric disorders. Numerous genetic modelling studies in mice demonstrate that Nrg1 signalling is important in the development of normal neuronal connectivity. Recent studies have identified novel signalling mechanisms and revealed unexpected roles of Nrg1 isoforms in both the developing and adult nervous system. Of particular interest to this discussion are findings linking deficits in Nrg1-ErbB4 signalling to perturbations of synaptic transmission, myelination, and the survival of particular sets of neurons and glia.