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Minimising the harm from inappropriate prescribing in older populations is a major urgent concern for modern healthcare systems. In everyday encounters between prescribers and patients, opportunities should be taken to identify patients at high risk of harm from polypharmacy and reappraise their need for specific drugs. Attempts to reconcile life expectancy, comorbidity burden, care goals and patient preferences with the benefits and harms of medications should be made in every patient at significant risk. Drugs identified by this process of reconciliation as conferring little or no benefit and/or excessive risk of harm should be candidates for discontinuation. Evidence supporting a structured approach to drug discontinuation (or deprescribing) is emerging, and while many barriers to deprescribing exist in routine practice, various enabling strategies can help overcome them.