Clinical benefit of antiplatelet therapy is established for cardiovascular disease and percutaneous coronary intervention (PCI). Dual antiplatelet therapy is used to optimize platelet inhibition. However, cardiovascular events still occur. Aspirin/clopidogrel resistance and poor compliance are the main factors implied in recurrent events. Compliance to dual antiplatelet therapy is particularly relevant during the first 6 months following acute coronary syndromes and PCI. Furthermore, several studies have shown association between antiplatelet resistance and poor compliance. Additionally, late (1 month to 1 year) and very late (> 1 year) stent thromboses are intimately linked to interruption of antiplatelet treatment. In this article we review the latest data about compliance, resistance and recommendations regarding antiplatelet therapy.