In this issue of Blood, Liao et al report that kindlin-2 is necessary for angiogenic sprouting in vitro and for developmental and tumor angiogenesis in vivo. The process of blood vessel sprouting is known to involve the αVβ3 vitronectin integrin on endothelium. Kindlin-2 linkage to the C-terminal tail of β3 completed the outside-in circuit necessary for integrin signaling that is critical for navigation of new vessel sprouts.