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Drugs are widely used and highly effective in the treatment of heart disease. Nevertheless, in some instances, even drugs effective in a population display lack of efficacy or adverse drug reactions in individual patients, often in an apparently unpredictable fashion. This review summarizes the genomic factors now known to influence variability in responses to widely used cardiovascular drugs such as clopidogrel, warfarin, heparin and statins. Genomic approaches being used to discover new pathways in common cardiovascular diseases and thus potential new targets for drug development are described. Finally, the way in which this new information is likely to be used in an electronic medical record environment is discussed.