Polypharmacy, the use of multiple medications, is commonly prescribed in the elderly but leads to reduced compliance with drug treatment regimens and increased risk of adverse drug reactions. This study was performed to systematically review the results of previous studies to assess the effects of interventions to improve prescription quality on reduction of the number of medications in elderly patients with polypharmacy, and to determine the most effective types of intervention in such cases. Relevant articles in the English language literature were retrieved by keyword searches on MEDLINE, the Cochrane Library, and cited references. The criteria for inclusion in this review were as follows: 1) studies in elderly subjects taking multiple medications or frail elderly subjects assumed to be taking multiple medications; 2) study interventions were intended to improve quality of drug use; 3) changes in the number of medications prescribed during the intervention period were reported; 4) the study designs were controlled clinical studies. Twenty-seven articles, including 28 controlled studies, matched all the inclusion criteria. The interventions in the studies included in the review were categorized into two groups: a medication review by medical professionals (26 studies); and a request to prescribing physicians for re-evaluation of the drug use for their patients (2 studies). Medication reviews by medical professionals, mainly pharmacists, resulted in a significant reduction of prescribed drugs (median, 0.45 drugs; 95%CI, 0.11-0.76). The differences in effects among intervention methods could not be investigated because of a lack of diversity in the methods used.