Malaria remains an important cause of global morbidity and mortality. As antimalarial drug resistance escalates, new safe and effective medications are necessary to prevent and treat malarial infection. Tafenoquine is an 8-aminoquinoline antimalarial that is presently under development. It has a long half-life of approximately 14 days and is generally safe and well tolerated, although it cannot be used in pregnant women and individuals who are deficient in the enzyme glucose-6-phosphate dehydrogenase. In well-designed studies, tafenoquine was highly effective in both the radical cure of relapsing malaria and causal prophylaxis of Plasmodium vivax and P. falciparum infections with protective efficacies of > or = 90%. Given its causal activity and safety profile, tafenoquine represents a potentially exciting alternative to standard agents for the prevention and radical cure of malaria.