Human schistosomiasis is a major neglected tropical disease that remains endemic in numerous countries of the tropics and subtropics. Controlling the transmission of schistosomes in their intermediate snail hosts remains a key challenge in the fight against schistosomiasis. Divergence in species, biogeography, and genotype in schistosomes and their intermediate hosts has resulted in diverse parasite-host interactions. This review focuses on recent insights in the biogeography and diversity of schistosome species and their snail hosts, and the molecular basis of compatibility polymorphism between them.