Tissue factor (TF) is a cellular receptor for coagulation factor VIIa (FVIIa), and the assembly of TF:FVIIa complexes on cell surfaces not only triggers the coagulation cascade but also transduces cell signaling via activation of protease-activated receptors. This brief review summarizes recent controversial data on the importance of protein disulfide isomerase-mediated disulfide bond switching in extracellular domain of TF in regulating its coagulant and cell-signaling activities. The review also discusses the importance of TF localization in lipid rafts and caveolae in maintaining its coagulant and signaling functions.