Older adults taking 5 or more medications daily (i.e., polypharmacy) face numerous challenges to taking them safely. In this study, patients, caregivers, and clinicians describe methods to taking medications safely, difficulties they face, and ways prescribers and pharmacists can assist patients. Medication reviews, a common strategy to ensure safe polypharmacy, were requested by patients to clear up confusion around generics, timing, limitations, and side effects.