Praziquantel is the only effective drug of choice against five human species of schistosomes. Main advantages of praziquantel include convenient oral administration, high safety and efficacy as well as short treatment course. To better understand the mode of action of praziquantel against schistosomes would be helpful for further development of new broad-spectrum anthelminthics. This paper summarizes the 30 years' research progress on the mode of action of the drug against schistosomes proceeded by domestic and abroad laboratories.