Pharmacotherapy of the elderly is very complex due to age-related physiologic changes, multiple comorbidities, multiple medications (prescription, over-the counter, and herbal), and multiple providers (prescribers and pharmacies). Age-related physiologic changes and disease-related changes in organ function affect drug handling (pharmacokinetics) and response (pharmacodynamics). In addition, patients' cognitive impairment, functional difficulties, as well as caregiver issues play a large role in errors and compliance. Many older adults have several chronic conditions, and they stand to benefit the most from best practice guidelines. However, they are also at risk of toxicity given our increasingly complex pharmacopoeia and potential adverse effects that can cause morbidity and mortality. It is imperative that physicians learn how to minimize side effects and interactions. Potentially inappropriate medications (medications that pose more risk than benefit to the patient) are among the most important causes of adverse drug reactions, independent of the number of medications and other confounding factors. Many of these adverse drug reactions could be predicted from the known pharmacology of the drug and therefore could be potentially avoidable. To prescribe appropriately, we need to consider not only the pharmacological properties of the drugs, but also clinical, epidemiological, social, cultural, and economic factors. Elders' adherence to prescribed medications is also complex and depends on medical, personal, and economic factors; cognitive status; and relationship with the physician. Detection of nonadherence is a necessary prerequisite for adequate treatment, and patient education is a cornerstone in achieving medication adherence. Finally, appropriate prescribing should include a consideration of life expectancy and goals of care.