Multiple medication use is common in older adults and may ameliorate symptoms, improve and extend quality of life, and occasionally cure disease. Unfortunately, multiple medication use is also a major risk factor for prescribing and adherence problems, adverse drug events, and other adverse health outcomes. Using the case of an older patient taking multiple medications, this article summarizes the evidence-based literature about improving medication use and withdrawing specific drugs and drug classes. It also describes a systematic approach for how health professionals can assess and improve medication regimens to benefit patients and their caregivers and families.