Tissue factor (TF), a transmembrane glycoprotein, is the main initiator of the blood coagulation cascade. TF is also recognized as a true signaling receptor. There is accumulating evidence that the downstream signaling effects of the TF complexes are transduced by several mechanisms, including: activation of protease-activated receptor (PAR)-1 and PAR-2, and the PAR-dependent pathways, via the TF cytoplasmic domain and by transactivation of receptor tyrosine kinases. Triggering of signaling cascades such as the mitogen-activated protein kinase and phosphoinositide 3-kinase/AKT pathways couples TF to a multitude of functions within the cell, such as proliferation, cell migration, and survival. Thus, TF has a Janus face; on the one hand, it has vital life-maintaining functions, and on the other it has harmful effects, exemplified by inflammation, the acute coronary syndromes, and cancer. TF mediates a broad spectrum of signaling mechanisms. Learning more about these different mechanisms/pathways will lead to new treatment strategies, which can ultimately be personalized.