IntroductionPolypharmacy and multimorbidity pose escalating challenges. Despite numerous attempts, interventions have yet to show consistent improvements in health outcomes. A key factor may be varied approaches to targeting patients for intervention.ObjectivesTo explore how patients are targeted for intervention by examining the literature with respect to: understanding how polypharmacy is defined; identifying problematic polypharmacy in practice; and addressing problematic polypharmacy through interventions.DesignWe performed a scoping review as defined by the Joanna Briggs Institute.SettingThe focus was on primary care settings.Data sourcesMedline, Embase, Cumulative Index to Nursing and Allied Health Literature and Cochrane along with ClinicalTrials.gov, Science.gov and WorldCat.org were searched from January 2004 to February 2024.Eligibility criteriaWe included all articles that had a focus on problematic polypharmacy in multimorbidity and primary care, incorporating multiple types of evidence, such as reviews, quantitative trials, qualitative studies and policy documents. Articles focussing on a single index disease or not written in English were excluded.Extraction and analysisWe performed a narrative synthesis, comparing themes and findings across the collective evidence to draw contextualised insights and conclusions.ResultsIn total, 157 articles were included. Case-finding methods often rely on basic medication counts (often five or more) without considering medical history or whether individual medications are clinically appropriate. Other approaches highlight specific drug indicators and interactions as potentially inappropriate prescribing, failing to capture a proportion of patients not fitting criteria. Different potentially inappropriate prescribing criteria also show significant inconsistencies in determining the appropriateness of medications, often neglecting to consider multimorbidity and underprescribing. This may hinder the identification of the precise population requiring intervention.ConclusionsImproved strategies are needed to target patients with polypharmacy, which should consider patient perspectives, individual factors and clinical appropriateness. The development of a cross-cutting measure of problematic polypharmacy that consistently incorporates adjustment for multimorbidity may be a valuable next step to address frequent confounding.