The emergence of personalized medicine mandates a complete understating of DNA sequence variation that modulates drug response. Initial forays have been made in the cardiac arena, yet much remains to be elucidated in the pharmacogenetics of cardiac drugs. Most progress has been made in describing DNA sequence variation related to the anticoagulant warfarin and the antiplatelet drug clopidogrel. This includes a description of DNA sequence variation that underlies pharmacokinetic and pharmacodynamic variability, the impact of such variation on predicting hard outcomes, and the ability of genotypeguided prescription to facilitate rapid titration to a therapeutic range while avoiding unnecessary high plasma levels. Nuanced prescription will require a complete inventory of DNA sequence variants that underlie drug-related side effects.