Tissue factor (TF), originally discovered to initiate coagulation, is more recently recognized to be involved in other biological processes, such as migration and anti-apoptosis. TF-mediated signaling regulates gene expression and protein synthesis, leading to alterations in cellular behavior. The proteolytic activity of factor VIIa (FVIIa), beta-1 integrin interaction and protease-activated receptor (PAR) activation are some of the key events involved in TF signaling. Post-translational modifications of TF may regulate signaling but this remains elusive. In vivo studies have established that TF signaling severely contributes to processes like angiogenesis, cancer growth and inflammation. This review focuses on the mechanism underlying TF-mediated intracellular signaling with its related physiological and mainly pathological consequences.