Osteoarthritis (OA) is a chronic musculoskeletal disease characterised by the destruction of articular cartilage, synovial inflammation and bone remodelling. Disease aetiology is complex and highly heritable, with genetic variation estimated to contribute to 50% of OA occurrence. Epigenetic alterations, including DNA methylation changes, have also been implicated in OA pathophysiology. This review examines what genetic and DNA methylation studies have taught us about the genes and pathways involved in OA pathology. The influence of DNA methylation on the molecular mechanisms underlying OA genetic risk and the consequence of this interaction on disease susceptibility and penetrance are also discussed.