Millions of people in France are taking long-term treatments with the two main antiplatelet drugs, aspirin and/or clopidogrel. Most of these people are on a secondary preventive regimen after arterial thrombotic events such as myocardial infarction, stroke, or ischemic complications of lower limb arteriopathy. The term resistance is often a source of confusion. When used, its definition should be explicit. It would be probably be wiser to use a term such as "variable response" which is more widely accepted by specialists and researchers. It would be better to use the term variable platelet response since true pharmacological resistance is rare. The distinction may have clinical pertinence in terms of prognosis. An abundant amount of biological and clinical work in the literature has improved our understanding of the topic. Diverse tests for exploring platelet functions can be used to evaluate the biological impact of treatment. They should, in the near future, contribute to the implementation of guidelines or suggestions for optimal therapeutic modalities. Upcoming results of ongoing large-scale prospective studies will be needed before confirming the potential usefulness and clinical pertinence of these tests.