The formation of blood vessels begins when angioblasts aggregate and assemble into a network of endothelial tubes. This process starts in the mesoderm adjacent to endodermal tissue and requires a signal from the endoderm. Now, Vokes and co-workers(p. 4371) have identified sonic hedgehog (Shh) as this signal. Using in situ hybridisation in chicks, they show that Shh is expressed in the endoderm at the time of vascular tube formation. In mouse and quail, disruption of Hedgehog signalling, by inhibiting or mutating Smoothened, prevents proper tube formation. Furthermore, Shh rescues vascular development in chicks lacking endoderm, and, when added to mouse endothelial cells in culture, promotes vascular assembly. Together, these findings demonstrate that Shh is both necessary and sufficient for the formation of vascular tubes, and is the first identified growth factor to regulate vascular tube formation in vivo.