Tissue factor (TF), a transmembrane glycoprotein, functions as an essential activator of the serine protease factor VIIa. This enzymatic complex is considered to be the principal initiator of in vivo coagulation. Recent studies emphasize the role of the TF/VIIa complex in a number of pathophysiological processes, such as Gram-negative sepsis, coronary artery disease and neointimal hyperplasia after angioplasty. Monocytes/macrophages are important contributors to some of these diseases and there have been new insights into the biology of TF regulation in monocytes. In the light of its structural similarity to cytokine receptors, there has been frequent speculation that TF has a role in intracellular signaling, a suggestion that is supported by some recent studies that propose a true receptor function for TF.