Hookworm is a widely prevalent human parasite and an important contributor to anemia worldwide. Efforts to control hookworm in developing countries currently focus on chemotherapy, especially for school-aged children. Due to the high rates of post-treatment hookworm reinfection and other factors that limit the success of school-based chemotherapy programs, a vaccine would represent a major new tool in the control of hookworm. Recent developments in the molecular biology of hookworm have made it possible to develop a recombinant vaccine. As hookworms have fundamentally different epidemiologic and immunologic characteristics to viral and bacterial infections, special methodologic and statistical consideration is needed in clinical trial design and evaluation. There are many remaining obstacles and issues in the research, large-scale development and delivery of a vaccine for a disease that afflicts the poorest of the poor in developing countries. There is also a need to assess the cost–effectiveness of vaccination relative to chemotherapy programs. This review summarizes current progress in vaccine development and discusses some of these issues and ongoing efforts to overcome remaining challenges. Hookworm is a widely prevalent human parasite and an important contributor to anemia worldwide. Efforts to control hookworm in developing countries currently focus on chemotherapy, especially for school-aged children. Due to the high rates of post-treatment hookworm reinfection and other factors that limit the success of school-based chemotherapy programs, a vaccine would represent a major new tool in the control of hookworm. Recent developments in the molecular biology of hookworm have made it possible to develop a recombinant vaccine. As hookworms have fundamentally different epidemiologic and immunologic characteristics to viral and bacterial infections, special methodologic and statistical consideration is needed in clinical trial design and evaluation. There are many remaining obstacles and issues in the research, large-scale development and delivery of a vaccine for a disease that afflicts the poorest of the poor in developing countries. There is also a need to assess the cost–effectiveness of vaccination relative to chemotherapy programs. This review summarizes current progress in vaccine development and discusses some of these issues and ongoing efforts to overcome remaining challenges