Cell-cell and cell-ECM interactions are key events in morphogenic processes during developmental and reproductive phases, in immune defense, wound healing and tissue repair, or hemostasis. Their dysregulation plays a major role in the pathophysiology of cardiovascular diseases (atherosclerosis, restenosis, thrombosis) or angiogenesis-driven tumor progression. Protease cascades such as the plasminogen activation system are linked to cell adhesion and migration. The urokinase-type plasminogen activator (uPA) as well as its receptor (uPAR) has been found in a complex with β₁-, β₂-, and β₃-integrins, thereby allowing mutual interactions and regulatory processes between cell adhesion and proteolysis to occur. Moreover, both uPAR and PAI-1 are capable of binding to vitronectin, an adhesive extracellular matrix protein, that serves as ligand for vascular integrins in an RGD-dependent manner. This short review will focus on the molecular and functional interactions between the uPAR system and vascular integrins and discuss consequences for vascular cell functions.