Malaria causes morbidity in 300–500 million people each year and claims 2–3 millions lives annually, mostly children in sub-Saharan Africa. In 1983, the cloning of malaria antigens offered great promise for developing a viable subunit vaccine. However, an efficacious human vaccine is still not available. Immunological studies on how the host’s immune system interacts with the parasite and studies on the pathogenic aspect of Plasmodium have found that several factors can impede protection by current vaccines. These findings suggest a novel approach needs to be considered.