Fibrin generation occurs as the result of a wide variety of pathological conditions. Extraneous deposition of fibrin outside a wound or inflammatory locus can lead to severe circulatory and respiratory complications. Fibrin within the circulation is removed by the hepatic macrophage (Kupffer cell). While many mechanisms for macrophage fibrin binding have been delineated in vitro, the complete pathway for in vivo fibrin clearance has not been determined. This article reviews these varied mechanisms and describes in detail a novel potential fibronectin-dependent pathway for hepatic fibrin clearance.