In recent years significant progress has been made in our understanding of epigenetic control of a wide range of cellular processes. This has come about both through the concerted effort of the research community and through the development of technologies essential to the area. The importance of the epigenetic control of the immune system is becoming increasingly clear, and therefore epigenetics presents itself as an attractive, and potentially ground-breaking, entry point to tackle immune-mediated conditions. The advances in our understanding are in part due to the development of next generation sequencing technologies and chromatin immunoprecipitation. When combined, these approaches have allowed studies at the chromatin level to understand cellular responses to cell-external cues on a genome scale. This has contributed significantly to improved understanding of chromatin, its regulation through histone post-translational modification (PTM), and the enzymes and proteins involved in ‘writing’, ‘reading’ and ‘erasing’ these histone PTMs. In this review we focus specifically on the progress made in understanding the mechanisms involved in modulating histone methylation in the context of immunity and discuss the potential, and the challenges, presented by this exciting area for drug discovery.