Tissue Factor (TF) is a crucial initiator of the extrinsic coagulation cascade. TF is expressed on cells which are normally sequestered from blood. However, upon injury TF is exposed to the blood resulting in activation of the coagulation cascade. TF dependent generation of coagulation proteases also initiates intracellular signaling through protease activated receptors. Pathologic TF expression is found in patients with a number of different diseases. This review will describe the roles of TF in health and disease as well as discuss approaches to reduce pathologic TF expression.