The integrity of our bodies is under constant threat by external forces. Blood coagulation and inflammatory pathways are important, highly efficient defence systems that support health and well-being in both normal and challenged conditions. Being potentially dangerous for the own organism, they are kept under strict control by anticoagulant and anti-inflammatory mechanisms. Coagulation and inflammatory pathways are closely integrated by extensive crosstalk and tend to function in concert. They comprise a large number of cellular and molecular actors, which interact in extremely complex manners. A basic principle governing these interactions is the mutual activation of the pathways. Thus, the activation of coagulation leads to concomitant activation of inflammatory pathways, mirrored by the initiation of coagulation by inflammatory pathways. Efficient anticoagulant systems not only keep coagulation reactions under strict control but also exert control on inflammatory reactions. During inflammation, these anticoagulant/anti-inflammatory systems are repressed allowing full activation of coagulation and inflammation. Dysregulation of the delicate balance between these systems contributes to the pathogenesis of many diseases.