Schistosomiasis affects around 140 million people worldwide, with the highest impact on people living in low- or middle-income countries. Although the number of deaths due to schistosomiasis seems relatively low, there is a long-term health burden on patients with chronic or repeat infections. Many historical anthelmintic drugs approved for the treatment of schistosomiasis are no longer in use due to a lack of efficacy or intolerable side effects. Praziquantel remains the only available treatment, but it has some considerable disadvantages—suboptimal efficacy against juvenile worms and a potential risk of developing resistance. Despite an obvious need for alternative antischistosomals, no new treatment options have emerged in the last 40 years and there are very few drug discovery programs working in this area. To tackle schistosomiasis, there is a need to establish a community-agreed target product profile to outline desirable criteria for developing new treatments. Recognizing the clinical impact of schistosomiasis and identifying the key requirements will help inform drug discovery efforts.