The formation of capillaries from preexisting blood vessels (angiogenesis) occurs in a variety of normal and pathological conditions, including organ development, would healing and tumor growth. Angiogenesis requires a strict temporal modulation of opposing cell functions: cell proliferation and migration, and extracellular matrix (ECM) degradation in the initial steps; arrest of cell proliferation and migration, ECM deposition and morphogenesis in the final steps. In the initial steps of angiogenesis, microvascular endothelial cells behave similarly to invasive tumor cells, as they cross basement membranes and interstitial stroma and invade adjacent tissues. However, unlike tumor invasion, the invasive process that occurs during angiogenesis is spatially and temporally restricted. As for tumor cell invasion, proteinases are of fundamental importance for the degradation of the perivascular ECM and endothelial cell invasion into the tissue to be vascularized. A number of studies have shown that, among the proteinases involved in angiogenesis, components of the plasminogen activator (PA)-plasmin system play a central role in endothelial cell migration and invasion.