The human malaria parasite, Plasmodium falciparum, ages the red blood cell during its intracellular development. During this process of erythrocyte senescence the parasitized cell becomes less dense and deformable, its biconcave disc shape becomes more spherical and is covered with microscopic protuberances (knobs); the amounts of membrane cholesterol and phospholipids are altered and phosphatidylserine (PS) is externalized. The malaria-infected cell is osmotically fragile, more permeable to a wide variety of molecules via new permeation pathways (NPP), and there is surface deposition of immunoglobulins and complement. There are declines in sialic acid, reduced glutathione, tocopherol and ATP. Hemichromes are deposited on the inner surface of the red cell membrane and there is clustering of the anion transporter, band 3 protein, as well as exposure of neoantigens which contribute to antigenic variation and adhesivity of the parasitized erythrocyte. These time-dependent changes result from oxidative assault and a combination of factors, including a decline in levels of anti-oxidants and ATP coupled with an enhanced flux of ions especially calcium. Despite these parasite-induced age effects P. falciparum is able to avoid destruction by splenic removal through microvessel sequestration in the deep tissues via PS, clustered band 3 protein and adhesive neoantigens.