The P. falciparum life cycle in humans includes the pre-erythrocytic stage, which initiates the infection; the asexual blood stage, which causes disease; and the gametocyte stage, which infects mosquitoes that transmit the parasite. At each of these stages, the parasite expresses proteins that are targets of malaria vaccine candidates (Tables 1–3). The pre-erythrocytic stage begins when a female Anopheles mosquito inoculates sporozoites into the skin or directly into the bloodstream. Sporozoites migrate to the liver and infect a small number of hepatocytes. A single sporozoite gives rise to tens of thousands of asexual parasites called merozoites. Merozoites exit the liver into the bloodstream approximately one week later, leaving no residual parasites in the liver. The pre-erythrocytic stage does not cause disease, and complete immunity to this stage is not induced through natural P. falciparum infection. Merozoites entering the bloodstream begin a cycle of erythrocyte invasion, replication, erythrocyte rupture, and merozoite release that repeats approximately every 48 hours. Symptoms of malaria only occur during the blood stage of infection. Immunity that protects against disease but not infection per se can be acquired by individuals who are repeatedly infected in endemic areas. A small percentage of blood-stage asexual parasites convert to sexual forms, or gametocytes, which can infect mosquitoes. The mosquito stage is a potential target for transmission-blocking vaccines, as the parasite in the mosquito midgut is present extracellularly and in relatively small numbers. Possible immune mechanisms at each stage are indicated.