Malaria is a parasitic disease which takes approximately half a million lives every year. The unicellular parasites are transmitted by mosquitoes and mainly affect vascular blood flow by invading red blood cells (RBCs). The pathogenicity of malaria primarily results from substantial changes in the stiffness of infected RBCs and their ability to adhere to endothelial cells and other circulating blood cells, leading to a substantial disruption of normal blood circulation and inflammation of the vascular endothelium. Multiscale modeling of malaria has proved to contribute significantly to the understanding of this devastating disease. In particular, modeling on the level of single infected RBCs allows quantification of their mechanics, cytoadherence, and individual as well as collective behavior in blood flow. Recent modeling advances in this direction are discussed.We show how computational models inmalaria are validated and used for the interpretation of experimental observations or the establishment of new physical hypotheses. Such computational models have a strong potential to elucidate a number of physical mechanisms relevant for malaria and to aid in the development of novel diagnostic tools and treatment strategies. © Springer Nature Switzerland AG 2020.