A variety of stimuli cause cells to move (chemokinesis); some also tell them where to go (chemotaxis). The signalling mechanisms that drive these two types of migration – random and directed – are usually similar. Sergei Grando and co-workers show that in the case of acetylcholine, however, they differ significantly (see p. 5665). Acetylcholine regulates migration of keratinocytes in the skin by binding to nicotinic receptors (nAChRs). Grando and co-workers have used a combination of receptor antagonists, antisense oligonucleotides directed against different nAChRs and cells from nAChR-knockout mice to examine the underlying mechanisms. They demonstrate that the α3 nAChR subtype controls chemokinesis whereas the α7 subtype controls chemotaxis. Moreover, they find that α3-nAChR-induced chemokinetic signalling leads to activation of protein kinase Cδ (PKCδ), the GTPase RhoA and its effector ROCK. By contrast, α7-nAChR-induced chemotactic signalling involves conventional PKC isoforms, Ca2+, PI 3-kinase and the GTPases Rac and Cdc42. Since keratinocyte migration is central to wound healing and implicated in metastasis, these findings not only shed light on migration mechanisms but also have potential clinical implications.