Epigenetics as a modifiable risk factor in periodontal diseases has been investigated in light of the current knowledge of how chronic infection and inflammation can affect gene-specific epigenetic reprogramming in periodontal tissues. Epigenomic programming might be particularly sensitive to environmental influences, and a combination of physiological stressors and environmental exposures appears to affect the epigenomic program acquired by a cell during differentiation and throughout the cellular lineage lifespan. Viral and bacterial infections can establish several types of epigenetic modifications, which sometimes engage in a complex epigenetic crosstalk also reflecting in the establishment and progress of periodontal diseases. The inflammatory and metabolic states of the periodontal tissues are driven by the infectious stimuli, and the magnitude of the cellular and molecular signature response is further dictated by the host genetic and epigenetic traits associated with various systemic exposures, including smoking, obesity and diabetes/hyperglycemia. This review discusses the advances in epigenetics, focusing on the role of DNA methylation in the pathogenesis of periodontal disease and the potential of epigenetic therapy.