After some 20 years experience it is generally agreed that chemotherapy against schistosomiasis, a parasitic disease which should be considered a consequence of a chronic infection, does have significant limitations. In particular, chemotherapy does not affect transmission of the infection or the high re-infection rates and so limits the success by demanding frequently re-scheduled mass treatments. For this reason, a complementary approach that can be integrated and could sustain chemotherapy-based control programs, i.e. vaccination, is very much needed. The rationale is that drug treatment would provide short-term reduction of worm burdens and vaccination, long-term protective immune response. Vaccination can either be targeted towards the prevention of infection or to the reduction of parasite fecundity. A reduction in worm numbers is the “gold standard” for anti-schistosome vaccine development but, as schistosome eggs are responsible for both pathology and transmission, a vaccine targeted on parasite fecundity and egg viability also appears to be entirely relevant. This review considers various aspects of anti-schistosome protective immunity that are important in the context of vaccine development. The current status in the development of vaccines against the African (Schistosoma mansoni and S. haematobium) and Asian (S. japonicum) schistosomes is then discussed as the new approaches that may improve on the efficacy of the available vaccines and aid in the identification of new targets for immune attack.