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Schistosomiasis is a notable neglected tropical disease caused by trematodes that infect mainly the intestines, bladder, and liver. Because of the unavailability of a schistosomiasis vaccine, control of the disease depends mainly on chemotherapy. Praziquantel (PZQ), which is active against all schistosome species (Among the five major species of human schistosomes−S. mansoni, S. haematobium, S. japonicum, S. intercalatum, and S. mekongi, S. mansoni is the most prevalent) as well as probably their hybrids and the recommended drug by the World Health Organization for schistosomiasis treatment at either the community or individual level, has become the exclusive drug because of its low cost and efficacy against the adult form of all schistosome species. In view of rapid re-infection following treatment and concern about the development of tolerance and/or resistance to praziquantel, there is an urgent need for research and development of novel drugs for the prevention and treatment of schistosomiasis. This comprehensive review shall attempt to briefly review the recent advances in the synthesis of antischistosomal drugs and agents in the literature from 1990s to now, particularly focusing on the context of potential development of antischistosomal agents. It shall be of interest for the pharmacologist.