Despite the identification of highly effective native antigens for vaccination against Haemonchus contortus, particularly 'hidden' antigens derived from the intestine of adult worms, to date similar efficacy has not been shown with recombinant antigens. In addition, progress towards identification of protective antigens from other sheep gastrointestinal (GI) nematode species is limited. Coupled with this is an incomplete understanding of the mechanism of natural immunity to GI nematodes, making selection of appropriate immunization strategies and adjuvants for evaluation of candidate 'natural' antigens problematic. The current explosion in new high-throughput technologies, arising from human studies, for analysis of the genome, transcriptome, proteome and glycome offers the opportunity to gain a better understanding of the molecular pathways underlying pathogen biology, the host immune system and the host-pathogen interaction. An overview is provided on how these technologies can be applied to parasite research and how they may aid in overcoming some of the current problems in development of commercial vaccines against GI nematode parasites.