The sequencing of the schistosome genome and the establishment of techniques for RNAi and transient transfection in these parasites have opened the door for a reverse genetics approach to studying schistosomes. One of the most intriguing aspects of schistosome biology is the interaction of these parasites with the immune system. The immune response underlies the ability of the host to survive while infected and to eventually develop resistance to further infection. However, it is also instrumental in the development of disease due to its role orchestrating granuloma formation around tissue-trapped parasite eggs. While schistosomes have clearly evolved mechanisms for evading host immune responses, their normal development is, paradoxically, also dependent upon the presence of a normal immune system. This article will review recent advances in the development of tools for studying gene function in schistosomes, and discuss how these new tools may be exploited to investigate issues of key importance in the interaction of schistosomes with the host immune system.