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Diacerein is a symptomatic slow-acting drug in osteoarthritis (SYSADOA) and the active metabolite is rhein. It is a non-steroidal anti-inflammatory drug with unique pharmacological properties as anti-oxidant and anti-apoptosis. Diacerein has recently shown to have a potential role by mediating anti-inflammatory as well as anti-oxidant and anti-apoptosis in kidney injury, diabetes mullites, and a beneficial effect on pain relief. It may have a therapeutic role in cancer, ulcerative colitis, testicular injury and cervical hyperkeratosis. Furthermore, diacerein has a valuable addition in combination therapy as a synergetic agent. This review, the first of its kind, highlights the proposed roles of diacerein in osteoarthritis and discusses recent results supporting its emerging roles with a particular focus on how these new insights may facilitate the rational development of diacerein for targeted therapies in the future.