The diagnosis of the procoagulant system is routinely based on activated partial thromboplastin time (APTT) and PT results indicating only a bleeding tendency. Routine screening tests for thrombophilia providing an objective measure of the anticoagulant potential of the blood are still lacking. Only antithrombin is determined quite frequently. The recent findings of activated protein C (APC) resistance have demonstrated the importance of the PC anticoagulant system in inherited thrombophilia. A vast body of evidence from in vitro and animal experiments as well as from recent clinical studies is presented revealing that the PC system potential plays a major role in maintaining the hemostatic balance at a variety of clinical conditions. It is suggested that acquired defects in the PC system are an underestimated cause for clinically induced venous thrombosis. New screening assays for the PC system potential are presented, which already indicate quite well congenital as well as acquired interferences of the PC system potential.