Fibronectin, a major interstitial matrix protein with binding sites for a variety of molecules and with multiple biologic activities, may play an important role in certain parasitic diseases. Leishmania and Trypanosoma cruzi bind host fibronectin, which, in turn, facilitates their association with the cells they parasitize. Invasive Entamoeba histolytica and Schistosoma produce proteases that degrade fibronectin and other matrix proteins, presumably facilitating the breaching of intestinal mucosa and dermal barriers to infection. The granulomatous inflammation that accompanies tissue deposition of schistosomal eggs promotes excess matrix production and scar formation. Granuloma macrophages and fibroblasts secrete fibronectin, which may serve to recruit additional fibroblasts and also may aid in maintaining the structural integrity of the granulomas. These early findings suggest that parasite-fibronectin interactions may be a fertile area for further research.