The binding of plasma protein fibrinogen (Fg) to intercellular adhesion molecule-1 (ICAM-1) on endothelial cells mediates the attachment of leukocytes and platelets that may result in vascular occlusion. Fg:ICAM-1 interactions elicit an array of effects that could have implications in vascular pathology and inflammation. ICAM-1 expression is regulated during inflammation and upon Fg binding. The mechanistic model presented provides a framework to delineate the consequences of Fg binding to ICAM-1.