Optimal prescribing is critical to the goals of geriatric medicine of curing disease, eliminating or reducing symptoms, and improving functioning. However, prescribing decisions in older people are often complex. There is marked heterogeneity in health status and functional capacity amongst older people, who range from fit, active, independent individuals to those who are physically and mentally frail, with limited physiological reserve. Age-related changes in physiology affect drug pharmacokinetics and pharmacodynamics, and together with various pathological processes, increase the risk of adverse drug events (ADEs). This risk is heightened by prescription of multiple medications to treat multiple co-morbidities. Consequently, balancing safety and quality of prescribing for older people with appropriate treatment of all co-morbidities can be challenging.