Polypharmacy is an increasing problem in the care of multimorbide patients, and increases morbidity, mortality, hospitalization rates and costs. A promising intervention against polypharmacy is the systematic listing of all drugs taken by the patient with critical appraisal of indication, side effects, dosage and alternatives of every single drug. It is necessary to consider and to discuss priorities and preferences of patients in regard to treatment goals. A clear medication plan is needed after shared decision making with the patient. We present some helpful tools for this purpose. Further challenges besides an empathic communication with the patient are finding enough time in the clinical encounter, the integration of other health professionals and computer-assisted solutions in primary care practices and hospitals.