It is now evident that differences in the DNA sequence of genes involved with drug action can lead to interindividual differences in effectiveness and adverse reactions to therapeutic drugs. Pharmacogenomics raises the possibility that drug discovery and patient management could move from a 'one drug fits all' approach to one in which therapy is tailored to patients' genomes. Genetically modified mice that mimic human variation in drug response can provide one of the tools to move the field towards these goals.