Patients with diabetes mellitus are at increased risk of cardiovascular events. Despite advances in medical and interventional therapy, cardiovascular morbidity and mortality remains high in patients with diabetes. Although accelerated atherosclerosis has long been recognized as an underlying cause, recent studies suggest that changes in platelets and coagulation also play important roles. Patients with diabetes exhibit a prothrombotic milieu with hyperreactive platelets and coagulation abnormalities. Thus, prevention of cardiovascular events in patients with coronary artery disease (CAD) and diabetes involves a multifactorial approach including treatment of risk factors such as dyslipidemia, obesity, hypertension, hyperglycemia, and hypercoagulation. An impaired response to antiplatelet therapy has been consistently reported and optimization of this therapy seems appropriate to reduce the risk of cardiovascular events in these patients. In this review, platelet abnormalities are summarized together with an update of benefits and limitations of antiplatelet therapy in patients with CAD and diabetes.