Hookworms are gastrointestinal nematodes that infect almost 1 billion people in developing countries. The main clinical symptom of human hookworm infections is iron-deficiency anaemia, a direct consequence of the intestinal blood loss resulting from the parasite’s feeding behaviour. Although treatment is available and currently used for the periodic removal of adult hookworms from patients, this approach has not effectively controlled hookworm in areas of rural poverty. Furthermore, treated individuals remain susceptible to reinfection following exposure to third-stage infective hookworm larvae in the soil as early as 4–12 months after drug treatment. Therefore, a prophylactic vaccine against hookworm infection would provide an attractive additional tool for the public-health control of this disease. The feasibility of developing a vaccine is based on the previous success of an attenuated larval vaccine against canine hookworm. Several laboratory and field studies have explored the development of a human anti-hookworm vaccine, describing potential protective mechanisms and identifying candidate antigens, one of which is now in clinical trials. The current roadmap that investigators have conceived has been influenced by vaccine development for blood-feeding nematodes of livestock and companion animals; however, recombinant vaccines have yet to be developed for nematodes that parasitise animals or human beings. The roadmap also addresses the obstacles facing development of a vaccine for developing countries, where there is no commercial market.