Advances in the field of human genetics has made it possible to develop prevention strategies for rare genetic disorders and to tailor pharmacotherapeutic approaches to anticoagulation and certain cancers. However, it is still not clear how genetic variations influence the risk and outcome of common diseases. Data from genome-wide association studies is just beginning to answer these questions. In contrast, pharmacogenetic knowledge is frequently not yet translated into clinical practice, even though in some cases, particularly regarding drugs used in treatment of thrombotic diseases (e.g., coumarines, platelet aggregation inhibitors), it is already known that testing for genetic variants prior to pharmacotherapy may help to prevent severe adverse drug reactions or avoid therapeutic failure. In this review, we address the potential impact that genetic alterations in the genes for vitamin K epoxide reductase and some cytochrome P450 variants may have on therapeutic strategies in anticoagulation.