Antiplatelet drug resistance is a multifactorial phenomenon that affects a large number of cardiovascular patients with symptomatic coronary artery disease. Although unique definitions for aspirin and clopidogrel resistance are missing, there is growing evidence for a clinical importance of response to antiplatelet therapy. The prevalence for aspirin and clopidogrel resistance has been reported to be between 5 and 30% in literature. Moreover, recent data suggest a high rate of dual antiplatelet drug resistance. Although there are convincing data about an association of aspirin resistance and clinical outcome, little is known about the clinical relevance of clopidogrel hyporesponsiveness. This article reviews the evidence for the clinical impact of antiplatelet drug resistance, with particular attention on the clinical outcome of clopidogrel low response according to current clinical data. Additional systematic studies are needed to evaluate the effects of alternative antiplatelet therapies in patients identified as low responders.