Rosetting — the formation of clusters in which uninfected red blood cells (RBCs) aggregate around a central Plasmodium falciparum-infected RBC (iRBC) — promotes RBC sequestration in the microvasculature and is associated with severe malaria. The P. falciparum erythrocyte membrane protein 1 (PfEMP1) mediates the formation of rosettes with blood group O RBCs but not with group A RBCs, suggesting that another P. falciparum protein might participate in rosette formation. Now, Goel et al. show that P. falciparum-encoded repetitive interspersed families of polypeptides (RIFINs) are expressed on the surface of iRBCs and that RIFIN-specific antibodies disrupt group A rosettes, but not group O rosettes. Furthermore, transfection of parasites that were selected for their low ability to form rosettes with a RIFIN-encoding rif gene resulted in rosette formation with group A RBCs and led to their in vivo sequestration in the microvasculature of infected rats. These data suggest that P. falciparum uses PfEMP1 to form rosettes with group O RBCs and RIFINs to form rosettes with group A RBCs.