Plasmodium falciparum is the etiological agent of malaria tropica, the leading cause of death due to a vector-borne infectious disease, claiming 0.5 million lives every year. The single-cell eukaryote undergoes a complex life cycle and is an obligate intracellular parasite of hepatocytes (clinically silent) and erythrocytes (disease causing). An infection can progress to a wide range of pathologies, including severe anemia and cerebral malaria, which can lead to death. P. falciparum repeatedly replicates over the course of 48h inside erythrocytes, resulting in exponential growth and rapid disease progression. As the single most important infectious disease afflicting children, no other pathogen has exerted a higher selection pressure on the human genome. Over 20 polymorphisms, including the sickle-cell trait, have been selected in human populations, despite severe fitness costs, since they offer protection against fatal P. falciparum infections. No effective vaccine exists, but several curative treatments are available.