Polypharmacy, defined as the concurrent use of multiple medications, represents a major public health challenge affecting older adults worldwide. With advancing age and increasing prevalence of multimorbidity, older adults frequently consume five or more medications simultaneously, exposing them to significant risks including adverse drug reactions, drug-drug interactions, medication non-adherence, and increased healthcare utilization. The current review synthesizes evidence-based literature on polypharmacy in older adults, focusing on epidemiology, risk assessment strategies, clinical consequences, and multidisciplinary management approaches. A comprehensive search of PubMed, Scopus, and Cochrane databases from 2015 to 2024 identified 54 peer-reviewed publications addressing polypharmacy assessment tools, deprescribing interventions, and clinical outcomes. This review demonstrates that polypharmacy significantly increases the hazard of mortality by 21–30% and hospitalization by 39–61% in community-dwelling older adults (1–3). The American Geriatrics Society Beers Criteria and the Screening Tool of Older Person’s Prescriptions (STOPP) criteria are widely validated instruments for identifying potentially inappropriate medications in this population. Pharmacist-led interventions, particularly medication reconciliation and deprescribing protocols, have demonstrated effectiveness in reducing medication burden, improving medication adherence, and enhancing quality of life (4, 5). A multidisciplinary team approach, incorporating geriatricians, family medicine physicians, clinical pharmacists, nurses, and laboratory specialists, has emerged as the gold standard for managing polypharmacy in older adults. This comprehensive review provides clinicians and healthcare professionals with current evidence-based strategies for optimizing medication management in elderly patients, thereby improving patient safety and clinical outcomes while reducing healthcare costs.