Patients with diabetes mellitus have much higher risk of developing cardiovascular disease. Diabetic patients with an acute coronary syndrome (ACS) have worse prognosis related to higher progression of atherosclerosis and blood hypercoagulability contributed by platelet hyperreactivity, increased coagulation marker and decreased fibrinolytic potential. Diabetic patients who present ACS derive greater benefit from complex antithrombotic therapy, particularly platelet-inhibiting therapies. Beneficial effects of antithrombotic drugs in diabetic patients with ACS have been demonstrated only for: prasugrel in ST-elevated myocardial infarction (STEMI) patients, glycoprotein IIb/IIIa receptor inhibitors in high-risk non-ST elevated myocardial infarction (NSTEMI) and STEMI patients undergoing PCI and for bivalirudin in STEMI patients. Taking into consideration available facts individualized treatment of patients with diabetes mellitus and coronary artery disease is crucial.