Older patients are at high risk of suboptimal prescribing (overuse, underuse and misuse of drugs), which can lead to serious adverse drug reactions (ADR). About one in four patients admitted to hospital are prescribed at least one inappropriate medication and up to 20% of all inpatient deaths are attributed to potentially preventable ADR. Lists of drugs to avoid (unnecessary or where risks outweigh benefits) and drugs not to be omitted (strong indications if there are no contraindications) can assist in identifying suboptimal prescribing although, to date, no trials have established the ability of such screening, by itself, to improve prescribing quality. Remedial strategies proven to be effective in randomized trials include detailed appraisal of medication lists by multidisciplinary teams, which involve geriatricians and close liaison with specialist clinical pharmacists. A multifaceted quality improvement strategy is proposed that includes an aspirational target of no more than five different drugs be regularly prescribed to vulnerable older patients. Achieving this target involves prioritizing drug selection on the basis of strength of indication which may run counter to current disease-specific clinical guideline recommendations based on trials that have excluded most older patients. Such a strategy is worthy of further evaluation in a multicentre randomized trial.