The process of angiogenesis (vessel formation) and the resulting stabilization of the mature vessel are complex events that are highly regulated and require signals from both serum and the extracellular matrix. Endothelial cells rest on a specialized thin extracellular matrix known as the basement membrane. Endothelial cells lining normal blood vessels are usually quiescent. When a proper stimulus is present, angiogenesis beings when endothelial cells degrade their basement membrane and invade the surrounding extravascular matrix. Formation of new vessels involves the migration and proliferation of cells. To assist the cells in their migration, the extravascular matrix provides an environment rich in stromal collagen fibers, fibrin, hyaluoronic acid, vitronectin and fibronectin. Once the endothelial cells assemble to form a new vessel, the cells secrete a basement membrane that helps to stabilize and maintain the vessel wall. The basement membrane adheres tightly to cells comprising the vessel wall, provides inductive signals, and plays a important role in the homeostasis of new vessels. We have demonstrated that two major components of the basement membrane, laminin and collagen IV, possess endothelial cell binding sites which regulate vessel stability. In this chapter, we will define the role of these molecules in endothelial cell behavior.