Achievement of a good quality of prescribing is one of the major challenges for physicians caring for older persons, because of aging-related changes in pharmacokinetics and pharmacodynamics of drugs, the large number of co-occurring chronic diseases affecting older adults and consequent polypharmacy. Several approaches are available and have been used to tackle over-prescription of drugs, such as medication review, application of appropriateness criteria and computerized prescription support systems, but, one by one, they have shown limited effectiveness with respect to patient-centred outcomes. We propose to test a multicomponent intervention with the goal of achieving the best-tailored pharmacotherapy for each patient at a specific point in time. The intervention should start with identification of patients at risk of drug-related problems and identification of their priorities, followed by medication review over time, supported by the use of inappropriateness criteria and computerized systems, and also necessarily embedded in the Comprehensive Geriatric Assessment.