Aging alters both the pharmacokinetic and the pharmacodynamic aspects of anesthetic requirement. Studies of the relationship between drug concentration and effect in older adults clearly demonstrate a decline in median effective dose requirement for agents that act within the central nervous system, but there appears to be little change in the dose required for peripheral effects such as neuromuscular blockade. Most drugs also undergo somewhat slower biotransformation and demonstrate prolonged clinical effects if they require hepatic or renal degradation, although many newer agents such as remifentanil and cisatracurium have organ-independent pathways that are not affected by age. In some cases, however, the appearance of increased sensitivity to a given dose of anesthetic or opiate may actually reflect higher-than expected plasma concentrations of drug following a rapid intravenous injection. Therefore, it is impossible to completely separate the interactions between pharmacodynamic and pharmacokinetic factors associated with aging. The use of pharmacological sympathectomy with intrathecal agents and with sympatholytic adrenergic agonists may further improve outcome in a patient population at high risk because of reduced functional reserve, increased incidence of polypharmacy, and the consequences of age-related disease.