Autoinflammatory diseases (AIDs) encompass a diverse range of conditions arising from defects or dysregulation within the innate immune system, characterized by recurrent or persistent inflammation and the absence of a primary pathogenic role for the adaptive immune system. Recent advancements in understanding AIDs pathogenesis increasingly implicate the significance of epigenetics. Although the precise role of epigenetic modifications in AIDs development remains elusive, it is hypothesized that while disease-causing single gene mutations initiate AIDs, epigenetic factors may modulate disease manifestations and outcomes. Similarly, epigenetic factors could influence the phenotypic expression and disease progression of complex AIDs. A comprehensive understanding of epigenetic contributions to AIDs may have the potential to predict individual disease outcomes and facilitate the development of novel, targeted therapies. In this chapter, we explore the current data elucidating the role of epigenetic factors in AIDs.