Substantial progress has been made in the last decade in identifying several antigens from Haemonchus contortus which, in their native form, stimulate useful levels of protective immunity (70-95% reductions in faecal egg output) in the ovine host. Much work has focussed on proteins/protein complexes expressed on the surface of the worm gut which are exposed to the blood meal, and, hence, antibody ingested with it. The antigens generally, but not in all cases, show protease activity and antibody is thought to mediate protective immunity by blocking the activity of enzymes involved in digestion within the worm. This review summarises the protective efficacy, as well as the biochemical and molecular properties, of the principal candidate antigens which are expressed in the gut of these parasites. Of course, such antigens will have to be expressed as recombinant proteins to be sufficiently cost-effective for use in a commercial vaccine and the current status of recombinant antigen expression is discussed with particular reference to conformation and glycosylation. There is a need for continued antigen definition even in the confines of gut antigens and potential targets can be selected from the rapidly expanding genome/EST datasets on the basis of predicted functional homology. Gene knockout technologies such as RNA interference have the potential to provide high throughput, rapid and inexpensive methods to define whether the protein product of a particular gene would be a suitable vaccine candidate.