The discovery that the nervous system plays a critical role in salamander limb regeneration, in 1823, provided the first mechanistic insights into regenerative phenomena and stimulated a long quest for molecular regulators. A role for nerves in the context of regeneration has been suggested for most vertebrate and invertebrate groups, thus offering a possible shared mechanism for the regulation of regenerative processes among animals. Methodological differences and technical limitations, especially in invertebrate groups, have so far hampered broad comparisons and the search for common principles on the role of nerves. This review considers both old and recent work in this topic and provides a broad perspective on the roles of nerves during regeneration. Nerves are found consistently to have important roles in regeneration, but their mode of action varies across species. The ongoing technological developments in a broad range of invertebrate models are now paving the way for the discovery of the shared and unique roles of nerves in animal regeneration.