The benefit of dual antiplatelet therapy with acetylsalicylic acid and clopidogrel in cardiovascular risk patients has been documented by several studies. Patients undergoing coronary interventions are in jeopardy of periinterventional thrombotic complications, and stent thrombosis, although a rare event, is still a serious problem, especially in the era of drug-eluting stents. Recently, there is a growing body of evidence that response to antiplatelet therapy is a clinically important entity and subjects presenting a low response to conventional antiplatelet substances are at increased risk for atherothrombotic events. Thereby, aspirin and clopidogrel resistance have been considered a multifactorial phenomenon underlying factors ranging from nonadherence of patients to antiplatelet therapy to demographic characteristics (age, diabetes, renal failure, etc.), acute coronary syndromes as well as genetic polymorphisms involving platelet glycoproteins and cytochrome P450 isoenzymes. The introduction of point-of-care platelet function tests into clinical routine is a still ongoing process, partly because of missing common definitions of resistance, partly due to different laboratory methods that prevent transferability of results. However, first approaches of an adoption of antiplatelet therapy guided by platelet function analysis provide promising results that an individualized antiplatelet strategy might help to improve platelet inhibition in cardiovascular patients. If this will improve clinical outcome has to be evaluated in upcoming studies. The aim of the present article is to give a review about the clinical relevance of resistance to antiplatelet therapy and alternative treatment options.