Epigenetic regulation is important in many facets of eukaryotic biology. Recent work has suggested that the basic mechanisms underlying epigenetic regulation extend to eukaryotic parasites. The identification of post-translational histone modifications and chromatin-modifying enzymes is beginning to reveal both common and novel functions for chromatin in these parasites. In this Review, we compare the role of epigenetics in African trypanosomes and humans in several biological processes. We discuss how the study of trypanosome chromatin might help us to better understand the evolution of epigenetic processes.