African trypanosomes infect humans and animals, causing disease and severely affecting the agriculture of rural sub-Saharan Africa. The trypanosomes are protected by a densely packed surface monolayer of variant surface glycoprotein (VSG). The haptoglobin hemoglobin receptor (HpHbR) within this VSG coat is used by the trypanosome for haem acquisition. HpHbR is exploited by the human innate immunity molecule, trypanolytic factor 1 (TLF1), which enters the trypanosome by binding the HpHbR. A collaboration between Mark Carrington’s lab and the labs of Matt Higgins in Oxford and Jayne Raper in New York, published recently in PNAS, has determined the structure of HpHbR, revealing an elongated three α-helical bundle with a small membrane distal head. The HpHb-binding site has been mapped and a single HbHpR polymorphism unique to human infective T. brucei gambiense has been shown to be sufficient to reduce binding of both HpHb and TLF1, modulating ligand affinity in a delicate balancing act that allows HpHb uptake but avoids TLF1 uptake. This work is important in understanding the human infectivity of T. brucei gambiense.