<i>Trypanosoma brucei</i> is the causative agent of African sleeping sickness in humans and one of several pathogens that cause the related veterinary disease Nagana. A complex co-evolution has occurred between these parasites and primates that led to the emergence of trypanosome-specific defences and counter-measures. The first line of defence in humans and several other <i>catarrhine</i> primates is the trypanolytic protein apolipoprotein-L1 (APOL1) found within two serum protein complexes, trypanosome lytic factor 1 and 2 (TLF-1 and TLF-2). Two sub-species of <i>T. Brucei</i> have evolved specific mechanisms to overcome this innate resistance, <i>Trypanosoma brucei gambiense</i> and <i>Trypanosoma brucei rhodesiense</i>. In <i>T. b. Rhodesiense</i>, the presence of the serum resistance associated (SRA) gene, a truncated variable surface glycoprotein (VSG), is sufficient to confer resistance to lysis. The resistance mechanism of <i>T. b. Gambiense</i> is more complex, involving multiple components: reduction in binding affinity of a receptor for TLF, increased cysteine protease activity and the presence of the truncated VSG, <i>T. b. Gambiense</i>-specific glycoprotein <i>(TgsGP)</i>. In a striking example of co-evolution, evidence is emerging that primates are responding to challenge by <i>T. b. Gambiense</i> and <i>T. b. Rhodesiense</i>, with several populations of humans and primates displaying resistance to infection by these two sub-species
