Praziquantel is the treatment of choice for schistosomiasis because of its efficacy, ease of administration, limited side effects, and low cost. Praziquantel has been so effective that alternative therapies are increasingly difficult to obtain, and the development of novel medications has been limited. The possibility of praziquantel resistance is a grave concern. Low cure rates for praziquantel have been reported in several countries, but despite widespread use, no significant loss of efficacy has occurred to date. The primary goal of antischistosomal therapy is parasite eradication, which reduces the likelihood of chronic complications, including advanced hepatic fibrosis. Mild to moderate hepatic fibrosis results from the immune response to schistosome eggs deposited in the portal venules and reverses with successful treatment. Most individuals clear schistosomiasis with a single course of therapy. Repeat doses cure the majority of patients in whom eradication does not occur after the initial dose. A secondary goal of therapy for patients with persistent or recurrent infection is egg burden reduction, which also reduces the risk of hepatic fibrosis and lowers community spread. Community eradication programs in highly endemic regions use periodic retreatment to limit chronic schistosomiasis' morbidity. Advanced liver fibrosis and portal hypertension due to chronic schistosomiasis are irreversible. Variceal bleeding is the primary cause of death in hepatic schistosomiasis. The bleeding risk is best reduced through use of beta-blocker prophylaxis or endoscopic banding or sclerotherapy. Surgical management of varices, including splenectomy with esophagogastric devascularization or selective shunts such as the distal splenorenal, is effective in patients with recalcitrant bleeding. Because hepatic synthetic function is normal in patients with schistosomiasis, procedures that reduce portal pressures may lower hepatic perfusion and cause hepatic impairment. The risk of encephalopathy after shunt surgery is higher in patients with schistosomiasis than in those with cirrhosis. For these reasons, nonselective shunt surgery such as the proximal splenorenal or the transjugular intrahepatic portosystemic shunt should not be performed in patients with advanced hepatic schistosomiasis.