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Over half of older adults experience polypharmacy, including medications that may be inappropriate or unnecessary. Deprescribing, which is the process of discontinuing or reducing inappropriate and/or unnecessary medications, is an effective way to reduce polypharmacy. This review summarizes (1) the process of deprescribing and conceptual models and tools that have been developed to facilitate deprescribing, (2) barriers, enablers, and factors associated with deprescribing, and (3) characteristics of deprescribing interventions in completed trials, as well as (4) implementation considerations for deprescribing in routine practice. In conceptual models of deprescribing, multilevel factors of the patient, clinician, and health-care system are all related to the efficacy of deprescribing. Numerous tools have been developed for clinicians to facilitate deprescribing, yet most require substantial time and, thus, may be difficult to implement during routine health-care encounters. Multiple deprescribing interventions have been evaluated, which mostly include one or more of the following components: patient education, medication review, identification of deprescribing targets, and patient and/or provider communication about high-risk medications. Yet, there has been limited consideration of implementation factors in prior deprescribing interventions, especially with regard to the personnel and resources in existing health-care systems and the feasibility of incorporating components of deprescribing interventions into the routine care processes of clinicians. Future trials require a more balanced consideration of both effectiveness and implementation when designing deprescribing interventions., (© 2022 The Association for the Publication of the Journal of Internal Medicine.)