The human genome project and related research initiatives have enabled the identification of a significant number of genetic variants that are predictive of drug response and outcome (pharmacogenomic biomarkers). As yet, incorporation of routine pharmacogenomic testing into clinical practice has been relatively modest. Potential barriers to adoption include a relative lack of prospective controlled trials establishing the benefits of such testing, economic constraints, and ethical concerns, among others. Clinicians considering the use of pharmacogenomic testing in their practice also may be unfamiliar with the concepts and principles underlying this rapidly evolving discipline. Consequently, the purpose of this review is to provide the clinical pharmacologist with a primer on the principles and molecular mechanisms underlying pharmacogenomics. In addition, the methods currently being used to discover novel pharmacogenomic biomarkers and then apply these to clinical practice will be described.