Individualization of drug therapy, described as tailoring drug selection and drug dosing to a given patient, has been an objective of physicians and other health-care providers for centuries. An understanding of the pathogenesis of the disease, the mechanism of action of the drug, and exposure-response relationships provides the framework for individualization. There are many approaches to individualization: selecting an antibiotic based on minimum effective concentrations and bacterial sensitivity, population (sparse sample) pharmacokinetics, therapeutic drug monitoring and, more recently, pharmacogenomics. The goal of individualization is to optimize the efficacy of a drug, minimize its toxicity, or both. With the growth of technology and databases, drug-disease-trial models and simulation have become useful for integrating information from many different domains. Physiology-based pharmacokinetic (PBPK) models have provided a mechanistic approach to individualization, and clinical trial designs such as those involving enrichment have also enabled individualization. In the future, "-omics" technologies, vaccines, ex vivo gene therapy, and the so-called "diseases-in-a-dish" will provide additional strategies to achieve individualization.