Polypharmacy, defined as the use of five or more medications, is a growing public health concern due to its risks. Deprescribing, the process of reducing or stopping inappropriate medications, is a key strategy to address polypharmacy. This review, based on literature from 2012–2022, explores clinicians' attitudes, barriers, and enabling factors in deprescribing for older patients with polypharmacy. Clinicians generally view deprescribing as complex, though many feel comfortable with it. Common barriers include lack of knowledge, time constraints, communication issues, and fear of adverse effects. Enabling factors include regular medication reviews, education, and a multidisciplinary approach. Patients often believe their medications are necessary but may want to reduce the number. Deprescribing can reduce harm, adverse events, and costs but faces challenges such as resistance from patients and healthcare providers. Barriers also include systemic issues like lack of time, limited resources, and unclear guidelines. Facilitators include patient education, clear communication, and structured approaches. Future directions emphasize education for both patients and clinicians, improving communication, and developing evidence-based guidelines. A multidisciplinary approach with pharmacists and specialists is crucial. Despite challenges, deprescribing is essential for managing polypharmacy in older adults.Polypharmacy, defined as the use of five or more medications, is a growing public health concern due to its risks. Deprescribing, the process of reducing or stopping inappropriate medications, is a key strategy to address polypharmacy. This review, based on literature from 2012–2022, explores clinicians' attitudes, barriers, and enabling factors in deprescribing for older patients with polypharmacy. Clinicians generally view deprescribing as complex, though many feel comfortable with it. Common barriers include lack of knowledge, time constraints, communication issues, and fear of adverse effects. Enabling factors include regular medication reviews, education, and a multidisciplinary approach. Patients often believe their medications are necessary but may want to reduce the number. Deprescribing can reduce harm, adverse events, and costs but faces challenges such as resistance from patients and healthcare providers. Barriers also include systemic issues like lack of time, limited resources, and unclear guidelines. Facilitators include patient education, clear communication, and structured approaches. Future directions emphasize education for both patients and clinicians, improving communication, and developing evidence-based guidelines. A multidisciplinary approach with pharmacists and specialists is crucial. Despite challenges, deprescribing is essential for managing polypharmacy in older adults.