Hedgehog (Hh) signalling controls cell fates and cell proliferation in many animals by regulating gene transcription. Some parts of the Hh pathway, including the final transcriptional effectors, are highly conserved. Thus, in flies and mammals, Hh signalling activates full-length Cubitus interruptus (Ci) and Gli family transcription factors, respectively, and prevents Ci/Gli proteolytic processing to repressor forms. But, are the molecules that regulate Ci/Gli protein activities similarly conserved? Steven Marks and Daniel Kalderon address this contentious topic on p. 2533 by investigating the regulation of mammalian Gli proteins in Drosophila cells. They show that the fly kinesin-family protein Costal 2 (Cos2), which directs Ci processing in Drosophila, binds to three regions of the transcriptional activator Gli1, just as for Ci, and that Cos2 silences mammalian Gli1 in Drosophila cells in an Hh-regulated manner. They also show that Gli regulation by protein kinase A is conserved between flies and mammals. Together, these results reveal a greater degree of Hh pathway conservation than was previously recognised.