Malaria remains a major cause of mortality in African children, with no adjunctive treatments currently available to ameliorate the severe clinical forms of the disease. Rosetting, the adhesion of infected erythrocytes (IEs) to uninfected erythrocytes, is a parasite phenotype strongly associated with severe malaria, and hence is a potential therapeutic target. However, the molecular mechanisms of rosetting are complex and involve multiple distinct receptor–ligand interactions, with some similarities to the diverse pathways involved in P. falciparum erythrocyte invasion. This review summarizes the current understanding of the molecular interactions that lead to rosette formation, with a particular focus on host uninfected erythrocyte receptors including the A and B blood group trisaccharides, complement receptor one, heparan sulphate, glycophorin A and glycophorin C. There is strong evidence supporting blood group A trisaccharides as rosetting receptors, but evidence for other molecules is incomplete and requires further study. It is likely that additional host erythrocyte rosetting receptors remain to be discovered. A rosette-disrupting low anti-coagulant heparin derivative is being investigated as an adjunctive therapy for severe malaria, and further research into the receptor–ligand interactions underlying rosetting may reveal additional therapeutic approaches to reduce the unacceptably high mortality rate of severe malaria.