Inappropriate prescribing of medicines may lead to a significant risk of an adverse drug-related event. In particular, prescribing may be regarded as inappropriate when alternative therapy that is either more effective or associated with a lower risk exists to treat the same condition. This review aims to identify interventions and strategies that can significantly reduce inappropriate prescribing in the elderly. The review is based on a search of electronic databases using synonyms of keywords such as 'elderly', 'interventions', 'optimized prescribing' and 'inappropriate prescribing' to identify reported interventions intended to improve inappropriate prescribing in the elderly. A total of 711 articles published in English were retrieved and considered. Of these, 24 original studies, involving 56 to 124,802 participants, met the inclusion criteria and were included in the systematic review. In 16 studies, the statistical power used to assess the impact of the intervention was >90% at a significance level of alpha=0.05. Various interventions were included in this study, such as educational interventions, medication reviews, geriatricians' services, multidisciplinary teams, computerized support systems, regulatory policies and multi-faceted approaches. Because of variability in assessment methodologies, mixed responses were found for education interventions aimed at improving inappropriate prescribing. For example, some studies did not assess what data were required to define whether a given level of intervention would be adequate, and others did not consider how many participants would be needed to demonstrate that a significant difference existed. Each of the three computerized support system interventions reported produced a significant enhancement in both prescribing and dispensing practices. Pharmacist interventions in community and hospital settings were evaluated in seven studies. However, variable criteria were used, with two studies using the Medication Appropriateness Index, another two studies using self-designed criteria for inappropriate prescribing, and the remaining three studies using Beers' criteria. A difficulty in assessing studies involving nursing home residents is that both consultant pharmacists and onsite pharmacist services may be involved, and, in one of the studies, only the role of the consultant pharmacist was considered. One of the most effective interventions appeared to be multidisciplinary case conferences involving a geriatrician, which resulted in a number of examples of reduced inappropriate prescribing in both community and hospital settings. As the effect of regulatory policies as an intervention is dependent on the target population involved, the effectiveness of this type of intervention was variable. Different strategies may be useful in reducing inappropriate prescribing in the elderly. It is not clear whether combined strategies undertaken simultaneously have a synergistic effect.