Pharmacotherapy represents one of the most important ways in which the practice of geriatric medicine differs from conventional medical care. The older patients is a major consumer of prescription and nonprescription medications, and proper use of these agents can lead to more cost-effective strategies in reaching optimal health. A key difference in distinguishing appropriate from inappropriate drug use is evident in the themes of polymedicine and polypharmacy. Polymedicine describes the use of medications for an older population for the treatment of multiple co-morbid conditions, while polypharmacy represents a less-than-desirable state with duplicative medications, drug-to-drug interactions, and inadequate attention to pharmacokinetic and pharmacodynamic principles. The purpose of this paper is to outline strategies toward optimal medication use as a key to successful aging. Specifically, we discuss themes of cost-effective prescribing, the role of medication compliance, overuse and underuse of medication, over-the-counter products, alcohol abuse, and preventive medicine. In addition, we discuss policy implications and responsibility for ensuring the high quality of pharmaceutical care. The reader should have a practical understanding of the pertinent issues in geriatric clinical pharmacology and its relationship to successful aging.