The frail elderly populations of nursing homes frequently use drugs and suffer from considerable comorbidities. Medication reviews are intended to support evidence based prescribing and optimise therapy. However, literature is still ambiguous regarding the optimal method and the effects of medication reviews. Innovative computerised systems may support the medication reviews in the future. We are developing a clinical decision support system (CDSS) that, independently of the prescribing software, continuously monitors all prescribed drugs while taking into account co-medication, laboratory-data and co-morbidities. The CDSS will be developed in five phases: (1) development of the computerised system, (2) development of the clinical rules, (3) validation of the CDSS, (4) randomised controlled trial, and (5) feasibility for implementation in different nursing homes. The clinical decision support system aims at supporting the traditional medication review.