Background: Variability in response to pharmacological treatment is one of the most important issues in the clinical practice at first exclusively attributed to clinical and demographic factors such as age, sex, nutritional status, alcohol abuse, smoking, presence of comorbidities and polypharmacy. Nowadays, it is well known that also genetic factors can modify the outcomes of pharmacological treatments. Polymorphisms in genes encoding molecules involved in both pharmacodynamics and pharmacokinetics may influence efficacy, tolerability, and safety of medications; thus, the knowledge of these genetic variants may help physicians to individualize and optimize the therapies.Objective: The main aim of this review is to summarize the current scientific evidence about cardiovascular pharmacogenomics. Conclusion: Cardiovascular pharmacogenomics is recommended only for some antiplatelet, anticoagulant and antihypercholesterolemic drugs thanks to standardized pharmacogenetic tests that are helpful in preventing thromboembolic and hemorrhagic events. Despite many studies have demonstrated that the application of pharmacogenetics may be useful also to individualize the therapy with other cardiovascular drugs, the paucity of large clinical trials and of cost-effectiveness studies limits the translation of such knowledge into clinical practice.