Osteoarthritis (OA) is the leading musculoskeletal cause of disability. Despite this, there is no consensus on the precise definition of OA and what is the best treatment to improve symptoms and slow disease progression. Current pharmacological treatments include analgesics, non-steroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX) inhibitors. None of those treatments are disease-modifying agents that target the core pathological processes in OA. Diacerein, a semi-synthetic anthraquinone derivative, inhibits the interleukin-1-beta (IL-1β) cytokine which, according to animal studies, plays a key role in the pathogenesis of OA. Diacerein was synthesized in 1980 and licensed in some European Union and Asian countries for up to 20 years. It has shown modest efficacy and acceptable tolerability in a number of trials of low to moderate quality. Early this year, the European Medicines Agency (EMA) conducted a review and restricted the use of diacerein-containing medicines. This was because of major concerns about the frequency and severity of diarrhoea and liver disorders in OA patients. In addition, the EMA's Pharmacovigilance Risk Assessment Committee (PRAC) questioned the limited clinical benefits of diacerein, which, in their view, did not outweigh its risks. The aim of this review is to provide a benefit-risk assessment of diacerein in the treatment of OA, based on asystematic evaluation of the published efficacy and safety data. Overall, there is evidence that diacerein is modestly effective for symptoms and possibly for radiographic changes, but this needs to be balanced against higher rates of gastrointestinal toxicity.