The transglutaminase (Tgase) family consists of nine known members of whom at least three are expressed in the vascular system: type 1 Tgase, type 2 Tgase and factor XIII. The cross-linking of proteins is a characteristic feature of Tgases, of well-known importance for stabilizing the blood clot and providing mechanical strength to tissues. However, recent data suggest that Tgases play a role in several other processes in vascular biology. These newly discovered areas include endothelial barrier function, small artery remodeling, and atherosclerosis.