There is limited geriatrics‐oriented clinical pharmacological information available to guide pharmacotherapy in late‐life psychiatric disorders. In this paper, we review available data on interindividual differences in drug exposure and central nervous system functioning, amplified by drug–drug interactions in the elderly, that may contribute to variable responses to treatment and significant adverse drug effects. The inclusion of greater numbers of elderly persons in clinical trials and the vigorous application of clinical pharmacologic methodology (i.e., pharmacoepidemiology, population pharmacokinetic modeling, and pharmacogenetics) will be critical for improving safety and personalization of drug and dose selection for elderly patients. Clinical Pharmacology & Therapeutics (2008); 85, 1, 89–93 doi: