During development inside red blood cells (RBCs), Plasmodium falciparum malaria parasites export a number of proteins beyond the confines of their own plasma membrane where they associate with the RBC membrane skeleton. Here they participate in protein-protein interactions with both RBC proteins and other parasite proteins and assemble into complex multi-component structures known as knobs. These interactions cause profound changes to the rheological properties of RBCs, particularly increased cell resistance to deformation and increased adhesiveness, which underpin the severe and often fatal clinical manifestations of falciparum malaria. Here, we bring together recent insights that have been made into understanding the molecular mechanisms that underlie these parasite-induced alterations to RBCs. We describe some of the well-established methods that have been used to quantify the altered rheological properties of parasitized RBCs (PRBCs) and discuss emerging techniques that have already begun to advance our knowledge of the molecular basis of this important human disease. Finally, we suggest potential new avenues for rheological anti-malaria therapy.