Pharmacogenetics is the study of the role of inheritance in variation in drug response phenotypes. Those phenotypes can range from life-threatening adverse drugs reactions at one end of the spectrum to equally serious lack of therapeutic efficacy at the other. Over the past half century, pharmacogenetics has--like all of medical genetics--evolved from a discipline with a focus on monogenetic traits to become pharmacogenomics, with a genome-wide perspective. This article will briefly review recent examples of the application of genome-wide techniques to clinical pharmacogenomic studies and to pharmacogenomic model systems that vary from cell line-based model systems to yeast gene deletion libraries. Functional validation of candidate genes and the use of genome-wide techniques to gain mechanistic insights will be emphasized for the establishment of biological plausibility and as essential follow-up steps after the identification of candidate genes.