Adverse drug reactions are common in persons aged 65 and older and are associated with increased morbidity and mortality. A heightened susceptibility to adverse reactions is due to a number of factors, including an increased incidence of disease, multiple drug use, and altered pharmacokinetic and pharmacodynamic properties of many drugs. The risk of drug interactions increases with the number of medications taken. Adverse drug reactions can be prevented through prudent prescribing practices, patient education, and adequate monitoring of drug efficacy and side effects. Several types of medications are of particular concern, including many antihypertensive agents, drugs with anticholinergic effects, psychoactive medications, and nonsteroidal anti-inflammatory drugs. Some drugs, such as histamine H2-receptor antagonists, are relatively safe but are overprescribed. Data regarding the risks associated with these problem drugs are presented, with recommendations for safe and effective treatment alternatives.