Background: Pharmacogenetics investigates the response to pharmacological treatments based on individual genetic background. Actually, numerous pharmacogenetic tests help to predict the response to drugs used in different medical areas, contributing to the so-called personalized medicine. Objective: This review aims to update the available data on the genotype-guided treatment with both the anticoagulant and antiplatelet agents. Moreover, it shed light on the pitfalls still contrasting the implementation of cardiovascular pharmacogenetics. Methods: A review of the literature on the studies investigating the effects of the genotype-guided anticoagulant and antiplatelet treatment was performed. Results: Considering the large use of antithrombotic drugs, pharmacogenetics has particular importance in this field. Several polymorphisms influence the response to both anticoagulant and antiplatelet agents, and tests, based on their identification, are now available. Conclusions: Recent randomized clinical trials demonstrated that pharmacogenetics might successfully contribute to optimizing the antiplatelet therapy also in patients particularly complicated to treat. However, despite accumulating evidence on the utility and feasibility of some pharmacogenetics tests, several barriers still contrast their implementation into clinical practice.