Since its first approval in 1997, clopidogrel has revolutionized interventional cardiology and transformed therapy for non‑ST‑segment elevation myocardial infarction (NSTEMI), STEMI, and percutaneous coronary intervention‑treated patients. It enjoyed a remarkable 15‑year "homerun" in the world market without any major competition. With the introduction of more potent P2Y12 receptor blockers, the current antiplatelet strategy is undergoing a transition period. Generic clopidogrel is inexpensive and pharmacodynamically effective in at least two thirds of the patients with coronary artery disease. The unpredictable, slow onset, and overall modest pharmacodynamic effects are the major limitations of clopidogrel. The new, more potent P2Y12 receptor blockers overcome the limitations of clopidogrel therapy and are associated with better clinical efficacy, but are more costly and associated with more bleeding. In this scenario, personalization of antiplatelet therapy based on platelet function and genetic testings to strike a balance between cost, benefit, and safety is a potential option.