Initiation of the coagulation cascade via exposure of active tissue factor (TF) to blood and formation of the factor VIIa/TF complex is essential for hemostasis and is an initial procoagulant signal in thrombosis. As of early 2012, over 20,000 articles listed on PubMed describe advances in the understanding of TF biology in the settings of hemostasis and thrombosis, as well as in signaling events in cancer, sickle cell anemia, hyperlipidemia, and a broad spectrum of inflammatory disorders. It is both inspiring and humbling, then, to consider not only what has been learned about TF regulation, but also the number of questions still remaining about its role in physiology. This supplement reviews both well-accepted and currently-controversial topics in coagulation and factor VIIa/TF biology, with particular foci on non-hemostatic roles of TF, innovative approaches for the treatment of hemophilia, and novel in vivo models of bleeding and thrombosis.