Diabetes mellitus has a major impact on cardiac morbidity and mortality with three major aspects of the relationship: (I) coronary multiple thickening and its consequences, (2) autonomic neuropathy of the heart, and (3) cardiomyopathy. It is well established that diabetic patients are more likely than patients without diabetes to die after an acute coronary syndrome (ACS). The increased mortality is seen both in the acute phase and during long term follow up. The unfavorable prognosis of diabetic patients has mainly been attributed to more pronounced left ventricular dysfunction and a high likelihood of reinfarction. Many factors may contribute to this unfavorable outcome, such as severe diffuse coronary artery disease, disturbed autonomic tone, diabetic cardiomyopathy, and abnormal platelet activation and thrombin-generation that are pronounced in diabetes, as well as purely metabolic factors causing more oxygen consuming use of free fatty acids during acute myocardial ischemia. There are many evidence-based interventions in ACS patients that are applicable to diabetic patients with ACS, and there are no specific contraindications to evidence-based therapies in patients with diabetes; thrombolysis and the use of beta-blockers should be used alongside other evidence-based therapies. The role of intensive intravenous insulin in diabetic patients with ACS remains to be clarified.