The older population represents the largest consumer group for medications. Age-associated pharmacokinetic and pharmacodynamic changes, reduced homeostasis, frailty, and drug-drug interactions increase the risk of adverse drug reactions (ADRs) in older patients. A better understanding of drug efficacy and safety profiles in this vulnerable group would help tailoring dosage and treatment monitoring before introduction into clinical practice. However, a very limited number of older subjects have participated in Phase I-III clinical trials hitherto. This chapter discusses the current knowledge on the main age-related changes in pharmacokinetics and pharmacodynamics, several important issues to be considered when planning and designing further pharmacokinetic and pharmacodynamic studies in older subjects, and recent regulatory documents on the conduct of such studies.