Antiplatelet therapy is essential for preventing thrombotic events in individuals with atherosclerotic cardiovascular disease (ASCVD). However, growing evidence suggests that the significant interindividual variability in response to antiplatelet agents, particularly the P2Y12 inhibitor clopidogrel, affects clinical outcomes and healthcare resource utilization. To achieve a better balance between bleeding and ischemic risks on an individual level, guided strategies for P2Y12 inhibitor selection utilizing platelet function testing have shown encouraging results. We hereby provide an overview of the rationale and supporting evidence for laboratory monitoring-guided antiplatelet therapy, highlighting the potential role in optimizing care for patients with ASCVD in the modern clinical landscape.