The prevalence of polypharmacy is very high in the nursing home setting. In this comprehensive review, we describe the many demographic, functional status, chronic disease, and healthcare financing factors associated with polypharmacy in nursing home patients. Recognition of the factors associated with polypharmacy is the first step for practitioners. A quality improvement intervention study previously conducted by the authors of this paper demonstrated that polypharmacy can be reduced in the nursing setting as a result of systematic review of medications by physicians.