Pharmacogenomics is a relatively recent yet rapidly expanding field of study examining how genetic variations influence responses to drugs. Antithrombotic drugs include the anticoagulant and antiplatelet compounds widely prescribed for the treatment and prevention of cardiovascular diseases. However, there is a large variability in response to antithrombotics, and this can modify the benefit/risk ratio of taking such medications. This variability can be explained by clinical factors such as age, sex, and drug-drug interactions, but also by genetic variants. In recent years, several genetic polymorphisms have been associated with variable biological responses to antithrombotics. Relevant polymorphisms related to antithrombotics have included target genes and genes that participate in the drugs' pharmacokinetics. This article provides a comprehensive review of the published literature about the pharmacogenomics of antithrombotic drugs, including well-studied compounds such as vitamin K antagonists (e.g., warfarin, acenocoumarol, and phenprocoumon), aspirin, and clopidogrel, as well as more recently approved compounds such as prasugrel, ticagrelor, and direct oral anticoagulants.