In this issue of Blood, Aird et al review recent findings that suggest the endothelial protein C receptor (EPCR), known for its pivotal role in mediating cytoprotection against coagulopathy, proinflammatory cytokines, and vascular permeability, may serve as a receptor for Plasmodium falciparum-infected red blood cells (IRBCs) in the brain. In the process, coagulation is allowed to proceed unchecked and contributes to the pathogenesis of cerebral malaria.