Schistosomiasis is a notable neglected tropical disease caused by trematodes that inflame 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 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 chemotherapy of schistosomiasis in the literature from 1990s to now, particularly focusing on the context of potential development of antischistosomal agents. Their antischistosomal properties, advantages, and disadvantages as well as structure-activity relationships are reviewed in a simple manner. It shall be of interest for both the synthetic chemist as well as the pharmacologist.