Schistosomiasis caused by trematode parasites, the Schistosoma bloodflukes, represents one of the most serious chronic infections in the developing world with more then 200 million people infected and many more at risk. Schistosomes reside in the portal and mesenteric or bladder and survive for many years producing hundreds of fertilized eggs per day. Chronic infections can persist for decades and severe morbidity results from host immune responses to eggs in tissues. Disease symptoms include; spleno- and hepatomegalies due to an immune-mediated entrapment (granulomas) of schistosome eggs, periportal fibrosis, portal hypertension, urinary obstruction, bladder carcinoma, sterility, malnutrition, developmental retardation. Resistant isolates of S. mansoni in some regions have been already reported from treated patients. Their evasive and immuno-modulatory strategies are key players in host-parasite interactions. Their bioactive molecules involved in these processes represent interesting subject for pharmacology. One group, proteases function at the host-parasite interface facilitating migration, immune evasion and digestion of host proteins. Besides of relatively well characterized enzymes there are groups of proteases which were surprisingly neglected. One of them is a group which belongs to the class of serine proteases, Clan PA trypsin-like family S1. These schistosomal proteases share similarities to several human regulatory factors such as mammalian kallikrein, epithelial transmembrane proteases, protein C-anticoagulation factor. This probably arose due to co-existence with the mammalian hosts and needs to actively interact with their physiological processes involving proteolysis (anticoagulation, vasodilatation, immuno-evasion). If hypothesis is valid, proteases may represent attractive bioactive pharmacokinetic molecules for further research. At last, it may have impact on better understanding of diseases, leading subsequently to new disease treatments.