Optimizing drug therapy is an essential part of caring for an older person. Prescribing in this group has unique challenges because of the high interindividual variability in pharmacological response and the fact that frailty, rather than age, predicts physiological responses to external stimuli. The effects of drugs and how they are handled by the body change in a number of ways with increasing age. With decreasing life expectancy, drugs used for secondary prevention might not be appropriate, particularly where their adverse effects lead to a reduction in short-term quality of life. The issue of polypharmacy is of particular concern in older people who, compared with younger individuals, tend to have more disease conditions for which therapies are prescribed. A number of drugs and combinations of drugs are particularly likely to cause harm to the older person with frailty, and these should be prescribed only where there is clear benefit. Unfortunately, the process of weighing the benefits and risks of drugs in this group is made more difficult by a paucity of directly relevant evidence. Formal criteria to identify potentially inappropriate medications have been developed, but can be cumbersome to apply and suffer from a lack of flexibility. Regular medication review is an important part of management of this patient group. Suggested strategies for this are discussed.