Coagulation proteases are involved in generating fibrin after vascular injury (hemostasis) but they also have multiple other effects, many of which are mediated independently of fibrin generation, via interactions with specific cell membrane-expressed "protease activated receptors". In inflammation, this family of proteins has a complex influence, the facets of which are still incompletely understood, though a common feature in different models appears to be amplification of innate signals that are initially generated by pathogenic elements or, in the context of transplantation, ischemia or anti-graft antibodies, for instance. There is increasing evidence that these proteases may also have specific effects on cells involved in adaptive immunity and on cells that mediate chronic inflammation and fibrosis. Understanding whether these effects are relevant in the responses generated against transplanted organs is important, as it could lead ultimately to the development of novel ways to promote long-term graft survival.