The Plasmodium life cycle comprises numerous transitions and stages, and any of these can be targeted by host immune responses. Upon inoculation by an Anopheles mosquito into the human dermis, elongated motile sporozoites must evade antibodies to (i) access blood vessels in the skin and then (ii) transit through liver macrophages and hepatocytes to initiate liver stage infection. Intrahepatocytic parasites (iii) are susceptible to CTLs. After approximately one week, infected hepatocytes rupture and release merozoites as aggregates called merosomes that might allow merozoites to (iv) evade antibodies and invade erythrocytes. Intraerythrocytic parasites (v) are susceptible to opsonizing antibodies and macrophages, and cytokine responses have been related to both protection and disease during this stage of infection. Antibodies that block (vi) binding of P. falciparum–infected erythrocytes to endothelium might prevent disease and control parasitemia. Human antibodies specific for (vii) sexual stage parasites are taken up by mosquitoes during the blood meal and can block transmission to mosquitoes, although these might require complement for parasite killing. Anopheles mosquito innate immune responses can also kill parasites during early (vii) or late (viii) sporogonic stages and lead to refractoriness to infection.