In case of coronary artery disease (CAD), diabetic patients are at higher risk than their non-diabetic counterparts. Antithrombotics are therefore of key importance to decrease the risk of ischemic complications. A careful assessment of the benefit-risk balance is however needed to limit the risk of bleeding. Diabetic CAD patients are characterized by a pro-thrombotic milieu and by an impaired response to both aspirin and P2Y12 receptor inhibitors, especially to clopidogrel. When combined with aspirin, the new P2Y12 receptor inhibitors prasugrel and ticagrelor provide superior efficacy for the diabetic patients with acute coronary syndromes. In stable CAD, antiplatelet monotherapy (aspirin) remains for the time being the reference treatment for diabetic as well as for non-diabetic patients; further studies are however ongoing to test whether the antithrombotic strategy should be reinforced, particularly in case of diabetes mellitus. Finally, although chronic oral anticoagulation is rarely indicated for CAD management in itself, it is often prescribed for the concomitant treatment of atrial fibrillation. The combination of anticoagulation and antiplatelet therapy is associated with a high risk of bleeding and should only be prescribed for limited periods of time when the estimated benefits exceed the risks.