Vasculogenesis and angiogenesis, the fundamental processes by which new blood vessels are formed, involve the proliferation, migration, and remodeling of endothelial cells. Dynamic adhesion of endothelial cells to extracellular matrix plays a fundamental role in all these events. Key regulators of endothelial cells adhesion and migration are the αvβ3 and uPA-uPAR complexes. The αvβ3 integrin heterodimer is the receptor for extracellular matrix components such as vitronectin and is overexpressed on the cell surface of angiogenic endothelial cells, but not quiescent cells lining normal vessels. The uPA-uPAR complex contributes to extracellular matrix remodeling by mediating proteolytic activity at the leading edge of migrating cells. We recently reported that the FOSL1 transcription factor of the AP-1 family plays a pivotal role in the regulation of the level of the αvβ3 and uPA-uPAR complexes on the surface of endothelial cells. In this commentary, we review the current knowledge of αv and β3 transcriptional regulation in endothelial cells and discuss the role of FOSL1 in angiogenesis.