Rho GTPases hit the headlines several times in 1990–1992: the proteins regulating their GTP–GDP cycle were identified and they were found to be key signal transducers, mediating growth factor-induced changes to the actin cytoskeleton and activating the phagocyte NADPH oxidase. Since then, they have been implicated in numerous cellular processes, from cell migration to cell survival, transcriptional regulation and vesicle trafficking. An explanation for why they affect so many aspects of cell behavior might lie in their ability to interact with a number of downstream targets, so that they can coordinately activate several molecular processes required for a particular cellular response.