Plasmodium falciparum is a protozoan parasite that causes the most severe form of human malaria. Five other Plasmodium species can also infect humans — P. vivax, P. malariae, P. ovale curtisi, P. ovale wallikeri and P. knowlesi — but P. falciparum is the most prevalent Plasmodium species in the African region, where 90% of all malaria occurs, and it is this species that causes the great majority of malaria deaths. These were reported by the WHO at 438 000 in 2015 from an estimated 214 million cases; importantly, however, figures for the global burden of malaria tend to have wide margins of error due to poor and inaccurate reporting. In this Perspective, features of P. falciparum that are unique among human malaria parasites are highlighted, and current issues surrounding the control and treatment of this major human pathogen are discussed.