Series Editor: Nigel Mackman Mark B. Taubman ATVB In Focus Tissue Factor: Past, Present, and Future Articles in this series: •Mackman N. Tissue factor: past, present, and future. Arterioscler Thromb Vasc Biol 2009;29:1986–1988. •Butenas S, Orfeo T, Mann KG. Tissue factor in coagulation: which? where? when? Arterioscler Thromb Vasc Biol 2009;29:1989–1996. •Bach R, Monroe D. Title. Arterioscler Thromb Vasc Biol 2009;29:1997–1998. •Schaffner F, Ruf W. Tissue factor and PAR2 signaling in the tumor microenvironment. Arterioscler Thromb Vasc Biol 2009;29:1999–2004. •Milsom C, Magnus N, Meehan B, Al-Nedawi K, Garnier D, Rak J. Tissue factor and cancer stem cells: is there a linkage? Arterioscler Thromb Vasc Biol 2009;29:2005–2014. •Hackeng TM, Rosing J. Protein S as cofactor for TFPI. Arterioscler Thromb Vasc Biol 2009;29:2015–2020. This issue of Arteriosclerosis, Thrombosis, and Vascular Biology contains 4 reviews on tissue factor (TF) and 1 on tissue factor pathway inhibitor (TFPI). One review on TF will be published in a later issue. In this editorial, we will briefly revisit the major advances in the field, highlight some of the current controversies, and discuss some of the future challenges. TF (also known as tissue thromboplastin or coagulation factor III) was first identified as a constituent of tissue that when added to plasma activated the clotting cascade—hence the name tissue factor. TF was first purified in 1985,1 and this subsequently led to the cloning of the TF cDNA and gene.2–5 In 1989 Drake and colleagues6 proposed that TF around blood vessels forms a “hemostatic envelope” that initiates clotting after vessel injury. The crystal structure of the extracellular domain of TF bound to Factor VIIa (FVIIa) was reported in 1996.7 In the same year it was discovered that inactivation of the mouse TF gene resulted in embryonic lethality.8–10 Taken together, these studies indicated that TF …