Introduction to the Theme “Context Is Everything: Defining the Factors That Contribute to Variability in Drug Response”

Drug response is shaped by far more than the interaction between a drug and its molecular target. The reviews in Volume 67 of the Annual Review of Pharmacology and Toxicology examine how temporal, pharmacokinetic, genetic, physiological, environmental, cellular, and psychosocial factors contribute to variability in drug efficacy, toxicity, and tolerability. This volume's reviews highlight emerging approaches for understanding these influences, including untargeted mass spectrometry–based technologies, artificial intelligence, and therapeutic drug monitoring, as well as the context-dependent actions of specific drug targets and physiological states. Together, these perspectives emphasize the dynamic and multifactorial nature of pharmacological and toxicological responses and the need to consider not only what a drug does, but also when, where, in whom, and under what conditions it acts.