Snails and schistosomes have a coevolutionary relationship spanning more than 200 million years [1]. Schistosomes are parasitic, with a life cycle alternating between a gastropod mollusc and vertebrate hosts (Figure 1). They have strong host specificity, particularly for the gastropod first intermediate host, in which they undergo their larval development [2,3], and which also dictates the geographical distribution of schistosomiasis (see Glossary) [4–۶]. Yet, not every encounter between a schistosome and a snail species deemed compatible results in the infection of the latter [7]. Understanding the basis of this compatibility polymorphism is the core interest of many studies investigating snail–schistosome interactions. Such knowledge is expected to be applicable in curtailing diseases caused by schistosomes through transmission blockade at the level of the snail host [2]. Several species of Schistosoma infect humans, but three are responsible for most of the infections: Schistosoma mansoni (infects Biomphalaria snails), Schistosoma haematobium (infects Bulinus snails), and Schistosoma japonicum (infects Oncomelania snails) [8]. Most studies of snail–schistosome interactions utilize the Biomphalaria glabrata–S. mansoni model [9]. From studies of this model, the snail’s immune response (Figure 2, Key Figure) has emerged as an important determinant of the success of S. mansoni infection, acting in concert with host and parasite genetics and epigenetics, proteomic and transcriptomic regulation, and environmental factors [10]. Stress-inducing environmental factors, particularly temperature, have been shown to influence B. glabrata susceptibility to S. mansoni [11–۱۳] by interfering with the capacity of the snail’s immune response to prevent parasite infection [11,12].