The sonic hedgehog (Shh) signalling pathway is a crucial mediator of cell proliferation, morphogenesis and fate, influencing the development and homeostasis of multiple organ systems during all stages of life. A central premise of Shh signalling is that the receptor patched 1 (Ptch1) mediates the Shh response, and that this response is greatest when Ptch1 is absent, allowing the release of pathway activator smoothened (Smo) and the eventual activation of Gli proteins. In this issue (p. 3331), Henk Roelink and colleagues challenge this notion by showing that cells devoid of Ptch1 remain Shh responsive in both transcriptional and migrational assays. Furthermore, the authors demonstrate a role for patched 2 (Ptch2) in mediating the Shh response in the absence of Ptch1, since a response to Shh is seen in Ptch1−/– but not in Ptch1−/–;Ptch2−/– cells. These data are indicative of a complex relationship between Ptch1 and Ptch2 in their regulation of Smo activity in response to Shh.