Polypharmacy in the elderly complicates therapy, increases cost, and is a challenge for healthcare agencies. In the context of the evolving role of the pharmacist, this systematic review examines the effectiveness of interventions led by pharmacists in reducing polypharmacy. A computerised search was conducted using Medline, Embase geriatrics and gerontology (2001 edition), the Cochrane Library and International Pharmaceutical Abstracts (IPA) databases. A manual search of articles on polypharmacy and the role of pharmacists in the therapy of the elderly and of the reference sections of all retrieved articles was also carried out. Search terms used were 'polypharmacy', 'elderly', 'aged', 'intervention' and 'pharmacist(s)'. Articles that fulfilled the following criteria were included: only elderly people were included in the study, or all ages were included but the study gave separate results for the elderly; the outcome was expressed as a reduction in the number of medications; a pharmacist participated in the study; and the study was a controlled or a randomised controlled study. We initially identified 106 articles, but only 14 studies met our four inclusion criteria. Reduction in the number of medications was not the major purpose of most selected studies but often a secondary outcome. Objectives differed, the general aim being to enhance the quality of prescribing in elderly patients. These controlled studies argued in favour of the effectiveness of pharmacists' interventions, even though the number of medications eliminated was small. Most studies were not designed to demonstrate the impact of reducing the number of drugs on the clinical consequences of polypharmacy (nonadherence, adverse drug reactions, drug-drug interactions, increased risk of hospitalisation, and medication errors). The most frequently reported outcome related to cost savings. It was therefore difficult to assess whether the interventions benefited the patient. The methodological quality of many identified studies was poor. In particular, the study objectives were often very broad and ill-defined. Polypharmacy itself has been defined in different ways and the appropriate definition may differ according to the patient population and the study setting. Further studies are needed to find the most effective way to reduce polypharmacy, especially in the frail elderly population, and to quantify the real advantages of simplifying their drug regimens in terms of improved quality of life.