Polypharmacy and inappropriate prescribing are common among nursing home residents with dementia. In many cases, medication is not discontinued despite the very limited life expectancy of these individuals, the increased risk of side effects due to drug-drug and drug-disease interactions, and the questionable benefits of medication. A structured approach is essential to managing the medication of nursing home residents with dementia. To facilitate rational prescribing, the WHO six-step method should be used. But it is also important to perform periodical medication reviews in which the appropriateness of the total medication set is evaluated. These medication reviews should be performed in a systematic manner in close collaboration between patient/caregiver, physician, and pharmacist. At the end of life, it can be expected that pharmacotherapeutic goals gradually chance from largely preventive to more symptomatic therapy. In this chapter, the problems related to polypharmacy are described. Guidelines, based on the WHO six step, are given on how to make rational choices when prescribing for individuals with dementia and on how to perform a medication review. Lastly, attention is given to issues concerning the stopping or withdrawal of medication.