Integrin cell adhesion receptors and their ligand fibronectin play important roles during disease-associated and developmental angiogenesis. However, there are many different integrins, each of which contains a specific α subunit and a specific β subunit, and it is not clear which α subunits are involved in angiogenesis. Now, Arjan van der Flier and colleagues implicate both α5 and αv integrins, the major endothelial fibronectin receptors, in vascular remodelling during mouse development (see p. 2439). The researchers first show that, unexpectedly, the endothelial-specific knockout of α5 integrin has no obvious effect on developmental angiogenesis. They then test whether αv integrins compensate for the absence of α5 integrins by generating endothelium-specific α5; αv double-knockout mice. Vasculogenesis and angiogenesis are initially normal in these mice, but subsequent remodelling defects in the great vessels and the heart eventually cause embryonic death. Further investigations into the complex interplay among integrins during angiogenesis revealed here could lead to the development of effective anti-angiogenic drugs for cancer therapy.