The present and increasing research evidence suggest that epigenetic mechanisms may hold great potential in the field of pain. The study was done for a systematic review of the literature exploring epigenetic mechanisms in people with pain. 4 databases have been interrogated following PRISMA guidelines in conducting study selection and assessment. Thirty-seven studies were included. Studies explored epigenetics in conditions such as fibromyalgia, CRPS, neuropathies, or osteoarthritis. The research focussed on genome-wide and gene-specific DNA methylation, and miRNA expression. Bioinformatics analyses exploring miRNA-associated molecular pathways were also performed. Several genes are already known for their role in pain, and several miRNAs linked to inflammatory regulation, nociceptive signaling, and protein kinase functions have been found to differ significantly between people with chronic pain and healthy controls. Although the studies included were cross-sectional in nature, and no conclusion on causal links between epigenetic changes and pain could be drawn, we summarised a large amount of data available in the literature on the topic, highlighting results that have been replicated by independent investigations. The field of pain epigenetics appears very exciting and has all the potential to lead to remarkable scientific advances. However, high-quality, well-powered, longitudinal studies are warranted.