The extracellular matrix (ECM) acts both as a physical scaffold for cells and as a repository for growth factors. Moreover, ECM structure and physical-chemical properties convey precise information to cells that profoundly influences their biology by interactions with cell surface receptors termed integrins. During angiogenesis, the perivascular ECM plays a critical role in determining the proliferative, invasive and survival responses of the local vascular cells to the angiogenic growth factors. Dynamic changes in both the ECM and the local vascular cells act in concert to regulate new blood vessel growth. The digestion of ECM components by proteolysis is critical for the invasive capacity of endothelial cells, but also creates ECM fragments, which antagonize the mechanosensory function of integrins, and can be apoptogenic. Here, we discuss the roles of integrins in modulating cellular responses to a changing ECM, in particular the regulation of survival and invasion among invasive endothelial cells.