Epigenetics, modifications of the DNA other than changes on the DNA sequences, is frequently studied in cancer research and aging. DNA methylation, mi-RNA, and histones deacetylation are investigated in different pathologies, including inflammatory diseases and age-related diseases such as osteoarthritis (OA). In this review, we focus on the chromatin-modifying enzymes in arthritic pathologies, and more particularly on Sirtuins. We also review the role of Sirt1 in OA, which has been highlighted in recent publications, and examine the possible protective role Sirt1 could play in this disease. Moreover, we discuss the possible therapeutic target of such a protein, reviewing the potential inhibitors/activators of this enzyme and their properties.