Activated platelets propel the vicious circle of inflammation. A procoagulant state or inflammatory process generating tissue factor (TF) may lead to platelet activation. Activated platelets bind to leukocytes promoting, in turn, leukocyte activation. Platelet leukocyte complexes produce chemokines that, when deposited on the vessel wall, facilitate leukocyte recruitment. Binding to leukocytes causes platelet P-selectin shedding. Elevated soluble P-selectin activates additional leukocytes. Activated leukocytes can produce leukocyte-derived microparticles (MPs) that further promote endothelial activation as well as cytokines and reactive oxygen species (ROSs) advancing inflammation and endothelial dysfunction. Endothelial dysfunction reduces NO and prostaglandin I2 production leading to increased release of WPBs promoting leukocyte and platelet rolling and facilitating platelet activation. Illustration by Marie Dauenheimer.