Although used for many years, a detailed understanding of the mechanism of action and metabolism of anticoagulants has become available only recently. After the addition of pharmacogenetic data to the drug label by the U.S. Food and Drug Administration, interest in the pharmacogenetics of warfarin and its clinical application has grown exponentially. Dosing algorithms have been developed and continue to be refined that incorporate the polymorphisms of P450 2C9 and vitamin K epoxide reductase. Widespread adoption of these algorithms has been slow because of factors such as physician education, timely testing, complexity of dosing calculations, dietary variations, and other confounding variables. Although most useful before the first dose, these tests are also being used to explain labile responses to warfarin. Current protocols are capable of predicting a large portion of interindividual dosing variation and, as more data become available, truly personalized dosing of warfarin should be achievable, improving patient safety and clinical efficacy.