Despite considerable progress in understanding the mechanisms of discordant xenograft
rejection, and overcoming hyperacute rejection through targeting of complement or
antibody, vascularized xenografts are typically rejected within days. Here, Fritz Bach and
colleagues discuss the importance of endothelial cell activation, platelet aggregation and
other aspects of thrombosis, as well as the contribution of host natural killer cell and
monocyte activation in overcoming this next barrier to prolonged xenograft survival.