Abstract: Antiplatelet therapy is of proven benefit to arterial thrombotic diseases. Although antiplatelet agents are usually given on fixed dosages, there is great interindividual variability in pharmacodynamic response to antiplatelet medications. Patients with high on-treatment platelet reactivity are at increased risk for thrombotic events. On the contrary, low on-treatment platelet reactivity has been linked to a higher risk of bleeding. Personalized antiplatelet treatment strategies based on platelet function monitoring constitute a promising tool for the prevention of both thrombotic and bleeding events, but the conclusive evidence for improved clinical outcomes with such approaches is yet lacking. Up to now, whether routine laboratory monitoring of antiplatelet therapy is of clinical benefit is still controversial. This review discusses the causes of variability in the response to aspirin or clopidogrel and highlights the current position of platelet function testing in guiding personalized antiplatelet therapy.