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As the older population in the U.S. continues to grow at an exponential rate and develops many of the medical conditions associated with aging, the reliance on multiple medications to address these issues has surged, resulting in increasing rates of polypharmacy. Broadly defined as the use of five or more medications at once, polypharmacy can have potentially harmful consequences for residents and negative financial implications for communities. In this guide, we explore polypharmacy in-depth, including its underlying causes. Steps to mitigate polypharmacy’s detrimental effects on resident outcomes and the financial burden it places on SL operators are also featured.