Podosomes are dynamic, actin-rich adhesive structures that are most commonly found in cells of the monocytic lineage. Most of our knowledge about podosomes, therefore, comes from studies performed in monocytic cells, and much less is known about podosomes that are formed in other cell types, such as the various subtypes of endothelial cell. In their study on page 2586, Elisabeth Génot and colleagues explore podosome formation in microvascular endothelial cells derived from capillaries to gain insights into their role in physiological angiogenesis. The authors identify two types of podosome: constitutive podosomes that form in adherent cells without specific stimulation and induced podosomes that arise in response to the canonical angiogenic factor VEGF-A. Both types of podosome share the same components, but VEGF-A-induced podosomes show enhanced gelatinolytic capacities compared with constitutive podosomes. Both laminin and collagen-IV, but neither collagen-I nor fibronectin, are conducive to podosome induction, indicating that extracellular matrix proteins are key determinants of the VEGF-A response. Moreover, in microvascular cells exposed to VEGF-A, only collagen-IV stimulates the formation of proteolytically active podosomes; the signalling mechanisms involve increased Src phosphorylation and MT1-MMP cell surface exposure at podosome sites, as well as p190RhoGAP-B relocalisation. This study offers new insight into VEGF-induced podosome formation and its function in endothelial cells.