Malaria is a mosquito-borne disease transmitted by inoculation with Plasmodium sporozoites. With approximately 2.4 billion people at risk, Plasmodium falciparum infection continues to be a major cause of mortality and morbidity, mainly in the tropics and subtropics. Although malaria-related morbidity and mortality have decreased in some areas due to improved treatment and the use of insecticide-treated mosquito nets, a vaccine is needed for sustained, effective, long-term control. Immunization with high doses of irradiated sporozoites has induced protective responses against malaria in human volunteers, An understanding of the immune mechanisms underlying the protection induced by irradiated sporozoites will pave the way for the development of subunit vaccines directed at the pre-erythrocytic stage of Plasmodium. To dote, RTS,S (GlaxoSmithKline), in combination with on effective adjuvant therapy, is the only vaccine candidate to demonstrate protection in humans in artificial challenge and natural environment trials. However, the protection afforded by this vaccine does not approach the level of sterile protection that is achievable with irradiated sporozoites. Strategies for improving its efficacy ore under development and it is likely that we will soon hove a second-generation multi-target malaria vaccine capable of inducing more powerful and long-lasting immune responses.