The development of subunit vaccines against most parasitic helminth infections will require a better understanding of the different components of a natural rejection process including (1) recognition of parasite antigens; (2) induction of protective immune response phenotypes; and (3) activation of appropriate immune effector mechanisms. While novel technologies have allowed significant progress to be made in the identification of candidate vaccine antigens, the large scale production of these antigens and their presentation to the host with appropriate adjuvant systems remains a major problem in vaccine research. Identification of the molecular interactions involved in the innate immune response to helminth infections and the application of new genomic and proteomic technologies are likely to lead to major advances in these research fields. Gastrointestinal nematode parasites and liver fluke are the most important helminth parasites of production animals. In recent years, a lot of new knowledge has been gathered on the immunobiology of the host-parasite interactions in these two infection systems, which has allowed new vaccination strategies to be considered. Functional genomic technologies such as gene expression analysis by microarrays, promise to further advance our understanding of the molecular pathways leading to protection against parasite infections. This will not only have implications for vaccine research, but also provide novel targets for drug development and genetic selection.