The use of combined antithrombotic medication in optimal dosages is mandatory for diabetic patients. Moreover, specific antiplatelet therapy in DM has been shown to reduce early and late atherothrombotic events in patients referred for elective and acute angiography and intervention as well as for secondary prevention of recurrent ischemic events in patients with coronary artery disease (CAD). Among these antiplatelet agents prasugrel has been recently demonstrated to lower adverse events in diabetic patients with acute coronary syndromes (ACS) significantly more effective than clopidogrel without increasing severe bleeding hazards. Also glycoprotein IIb-IIIa receptor inhibitors (GPI) had a greater effect in diabetic subjects with ACS undergoing percutaneous coronary intervention (PCI) on adverse clinical events compared to non-diabetics. In contrast to antiplatelet therapy, all commercially available antithrombins except enoxaparin have been shown to be equal or less effective in diabetics compared to non-diabetics. Enoxaparin was superior to unfractionated heparin (UFH) in reducing adverse events in diabetics with acute ST-elevation myocardial infarction (STEMI) undergoing thrombolytic therapy. The role of several new antithrombins, i.e. direct factor Xa inhibitors or direct antithrombins in diabetic patients with stable or unstable CAD is still under investigation.