This article explores polypharmacy and differentiates between appropriate and problematic polypharmacy. Issues associated with problematic polypharmacy, such as drug-to-drug interactions, adverse drug reactions, and underprescribing, are discussed. The concepts of compliance, concordance and adherence, which are terms commonly associated with patients following or not following treatment regimens, are explored. Medicine use review is explored as a holistic approach to optimizing medicines, promoting concordance, and achieving appropriate polypharmacy.