Personalized medicine is an emerging field with a goal of applying genomic 
information as a predictor of disease risk as well as individualization of drug 
therapy. For optimization of drug therapy, significant progress has been made in 
the past decade in linking genetic variation in genes associated with drug 
disposition to prediction of drug response and adverse reactions. For most drugs 
in clinical use, the interplay of many factors, including genetics, 
demographics, drug-drug interactions, disease states and the environment, result 
in the interindividual variability observed during drug therapy. Broadly 
speaking, such determinants of drug response are mediated through modulation of 
drug concentrations reflective of pharmacokinetic factors, as well as drug 
targets, often referred to as pharmacodynamics. It is clear that for 
personalized medicine to become clinically meaningful, genomic as well as 
clinical and environmental influences must be considered together. We show, for 
a number of drugs in clinical use, that genomics-guided treatment options not 
only are becoming feasible but are also on the cusp of showing superiority in 
terms of clinical outcomes as well as cost-benefit. One of the most widely 
studied drugs with regard to genomics-guided dosing options is the oral 
anticoagulant, warfarin. Genetic polymorphisms in the gene encoding cytochrome 
P450 2C9 (CYP2C9) and those in the target gene responsible for the warfarin 
anticoagulant effect, vitamin K epoxide reductase (VKORC1), account for much of 
the variability in the warfarin maintenance dose; however, routine genotyping in 
warfarin therapy remains controversial. We will outline the importance of 
understanding all of the variables that mediate warfarin response as the 
prerequisite to successful utilization of genotype-guided warfarin therapy. 
Similarly, HMG Co-A reductase inhibitors, commonly known as statins, also 
display wide interindividual variability in plasma concentration, response and 
toxicity due in part to polymorphisms in transporter genes, including SLCO1B1 
and ABCG2. Genetic factors are also important considerations in treatment with 
other therapeutic agents discussed, including clopidogrel and tamoxifen. 
Implementation of personalized medicine-based treatment options for these and 
other drugs, the pharmacokinetics or pharmacodynamics of which are impacted by 
functional genetic variations, will require overcoming a number of challenges, 
including cost, turnaround time, and demonstration of clinical benefit, as well 
as better training of health care professionals about genomics in general, and 
pharmacogenomics in particular.