This systematic review aimed to identify and summarize definitions of polypharmacy in existing literature. Polypharmacy, defined as the use of multiple medications, is common in older adults with multimorbidity, but lacks a consensus definition. The review searched MEDLINE, EMBASE, and Cochrane databases from January 1, 2000, to May 30, 2016, and identified 1156 articles, of which 110 met the inclusion criteria. Definitions were categorized into numerical only (using the number of medications), numerical with a duration or healthcare setting, and descriptive. The most common definition was five or more medications daily (46.4% of articles). Only 6.4% of articles distinguished between appropriate and inappropriate polypharmacy. The review highlights the need for a clear and universally accepted definition of polypharmacy to improve clinical assessment and management.This systematic review aimed to identify and summarize definitions of polypharmacy in existing literature. Polypharmacy, defined as the use of multiple medications, is common in older adults with multimorbidity, but lacks a consensus definition. The review searched MEDLINE, EMBASE, and Cochrane databases from January 1, 2000, to May 30, 2016, and identified 1156 articles, of which 110 met the inclusion criteria. Definitions were categorized into numerical only (using the number of medications), numerical with a duration or healthcare setting, and descriptive. The most common definition was five or more medications daily (46.4% of articles). Only 6.4% of articles distinguished between appropriate and inappropriate polypharmacy. The review highlights the need for a clear and universally accepted definition of polypharmacy to improve clinical assessment and management.