The role of Tissue Factor (TF, thromboplastin) as the major factor in initiation of the blood coagulation process has been known for more than 100 years. Its importance for the development of clinical thrombosis, be it venous or arterial, and the complexity of the cell biology of TF, have however been increasingly appreciated over the past 15-20 years. Acting as a cofactor for coagulation factor VIIa, it is now clear that TF is able to activate factor IX. Aberrant expression of TF seems to play a major role in the intravascular coagulations disorders linked to endotoxemia, malignancies, immunological diseases and atherosclerosis. Tissue Factor Pathway Inhibitor (TFPI) is the natural direct inhibitor of TF/FVIIa complex. In this study the physiological role, mechanism of action and pharmacological potential of TFPI are discussed.