This paper describes a method for the identification of host proteins that interact with pathogens, and provides an interesting set of such proteins for the snail Biomphalaria glabrata. Data have recently accumulated on an unexpected degree of specificity in the immunological interaction of invertebrate hosts with their pathogens and parasites. However, progress is often limited by the fact that different host species make use of diverse, and sometimes unique immunological sensors and effectors. Therefore, approaches that are based on comparison with model organisms and that often rely on an assumed homology of the immune system components might miss the specific molecules that are relevant in a particular host-pathogen system. In this context, the described method is most promising, since it is versatile and could be applied to many other hosts. It is based on the in vitro binding of cell-free host hemolymph (blood) proteins to diverse pathogens, followed by proteomic analysis. It is particularly interesting for non-model hosts and could provide a very useful complementation to, for example, transcriptomic studies of host-pathogen interactions. In B. glabrata, it is most interesting that several of the identified proteins are not 'classical' immune candidates. For example, biomphalysins are toxins that were most likely obtained by horizontal gene transfer in many eukaryotes, and were here shown to bind to all the pathogens tested. Other interesting examples are derivatives of hemoglobin that, for example, bind to trematodes.