Background Polypharmacy is common among older people and may be associated with adverse drug events (ADEs) and poor health outcomes. Pharmacists are well-positioned to reduce polypharmacy and potentially inappropriate medications. Objective The objective of this narrative review was to summarize the results from randomized-controlled trials that evaluated pharmacist-led interventions with the goal or effect to deprescribe medications in older individuals. Data Sources We searched Medline, Embase, CINAHL Complete, APA PsycInfo, Web of Science Core Collection, and Cochrane Central Register of Controlled Trials. Data Synthesis Of the 25 studies included, the interventions were conducted in nursing facilities (n = 8), outpatient/community dwellings (n = 8), or community pharmacies (n = 9). Interventions were categorized as comprehensive medication reviews (n = 10), comprehensive medication reviews with pharmacist follow-up (n = 11), and educational interventions provided to patients and/or providers (n = 4). Pharmacist-led interventions had a beneficial effect on 22 out of 32 total medication-related outcomes (eg, number of medications, potentially inappropriate medications, or discontinuation). Most (n = 18) studies reported no evidence of an effect for other outcomes such as health care use, mortality, patient-centered outcomes (falls, cognition, function, quality of life), and ADEs. Discussion Interventions led to improvement in 69% of the medication-related outcomes examined across study settings. Five studies measured ADEs with none accounting for adverse drug-withdrawal events. Large well-designed studies that are powered to find an effect on patient-centered outcomes are needed. Conclusion Pharmacist-led interventions had a significant beneficial effect on medication-related outcomes. There was little evidence of benefit on other outcomes.