In certain contexts, voltage gradients and ion flows are known to regulate developmental patterning, but their precise role has remained ambiguous. Now,Michael Levin and colleagues report on the role of the V-ATPase H+pump in Xenopus tail regeneration. Cells in an uncut tail have normal membrane potential levels. However, following the amputation of the tail, the regeneration bud becomes depolarised(p. 1323). Shortly after, V-ATPase expression is triggered, leading to H+ flux and to the rapid repolarisation of these cells. The genetic or biochemically induced loss of V-ATPase activity prevents tail regeneration, but not as a consequence of apoptosis. Axon patterning and tail outgrowth are restored if H+flux is induced. This fascinating study shows that ion flows do not simply perform housekeeping duties and that, during Xenopus tail regeneration,H+ flux controls both cell number (through membrane voltage) and correct axon guidance (nerves are a known growth-factor source) into the regenerative bud. Ion pumps provide a tantalising target for future biomedical research into regeneration.