Clopidogrel resistance is an emerging clinical scenario, as antiplatelet therapy has become the cornerstone of modern cardiovascular treatment. This leads to an increase in stent thromboses and recurrent ischemic events which add to the health care costs, and increased periprocedural morbidity and mortality. Management of clopidogrel resistance is challenging as there are no standardized guidelines. The arrival of newer antiplatelet drugs and the detection of genetic polymorphisms in susceptible populations may have an impact on the management. Further trials are needed regarding the target population who should be screened for clopidogrel resistance, a standardized diagnostic test to detect clopidogrel resistance, the role of pharmacogenetics, and the need for tailored therapeutic options for a patient with clopidogrel resistance.