A serine protease in human plasma termed hyaluronan-binding protease HABP is structurally related to plasminogen-activators, coagulation FXII and hepathocyte growth factor activator. This protease has coagulation and fibrinolysis-related activities, although a physiologic role in haemostasis still requires confirmation. In more recent years accumulating information became available supporting the hypothesis that HABP plays also a significant role in the regulation of cells in the vasculature and in the perivascular environment. On the one hand HABP generates bradykinin or bFGF on the surface of human umbilical vein endothelial cells (HUVECs), triggering intracellular signalling via the bradykinin receptor 2 and FGFR-1. Other data indicate that beside endothelial cells also vascular smooth muscle cells are a target for HABP. As major mechanism of cell regulation a high affinity of HABP to growth factors with the subsequent proteolytic cleavage and inactivation has been identified. The current knowledge of the physiologic and clinical relevance of HABP as a vascular and possibly inflammatory mediator is summarized in this review.