Pharmacogenomics is the use of genomic and other “omic” information to individualize drug selection and drug use to avoid adverse drug reactions and to maximize drug efficacy. The science underlying pharmacogenomics has evolved rapidly over the 50 years since it was first suggested that genetics might influence drug response phenotypes. That process has occurred in parallel with advances in DNA sequencing and other molecular technologies, with striking increases in our understanding of the human genome. There are now many validated examples of the clinical utility of pharmacogenomics, and this type of clinical genomic information is increasingly being generated in clinical laboratories, incorporated into electronic health records, and used to “tailor” or individualize drug therapy. This review will survey the origins and development of pharmacogenomics; it will address some of the challenges associated with the clinical implementation of pharmacogenomics; and it will attempt to foresee future advances in this important genomic discipline, one that almost certainly will be among the earliest and most widely adopted aspects of clinical genomics.