The use of antithrombotic agents, particularly antiplatelet drugs like aspirin and clopidogrel, has been instrumental in decreasing the risk for adverse cardiovascular events across a wide range of patients. However, despite the established benefits, the use of these medications remains suboptimal. There is a high degree of inter-individual variation in response to these treatments, whereby patients experience occlusive thromboembolic events, in spite of maintaining an appropriate treatment regimen. This has lead to the notion of antithrombotic "resistance" or "poor responders", which has been a growing concern amongst clinicians and other healthcare providers. Compounding this matter even further, reports of increased cardiovascular risk associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen, have revealed additional and unforeseen contributors to myocardial infarction and stroke. With all medications, striking a balance between the potential risks and benefits seems more art than science at times. However, given their widespread use and critical cardiovascular implications, further emphasis has been placed on understanding factors influencing antithrombotic and NSAID therapies. A major aim in cardiovascular pharmacogenetics is the discovery of genetic biomarkers that will allow for prospective screening and individualized prediction of drug efficacy and adverse reactions for these medications (both alone and together) within the context of cardiovascular disease.