Although many cross-sectional studies and a small number of randomized controlled trials have addressed the relationship between schistosomiasis and anemia, the conflicting results make the magnitude of the relationship unclear. In fact, only one randomized controlled trial that treated solely for schistosomiasis has demonstrated an impact of praziquantel on hemoglobin concentration. The potential mechanisms underlying a relationship between schistosomiasis and anemia are also unclear. In this article, we discuss four possible mechanisms that might mediate this relationship, based on animal and human models, including extra-corporeal loss of iron, splenomegaly leading to red blood cell sequestration, autoimmune hemolysis and anemia of inflammation.