Diabetes mellitus (DM) remains an important predictor for mortality in patients with ST-segment Elevation Myocardial Infarction (STEMI) although the use of reperfusion therapy has resulted in a considerable improvement of survival. Of importance, newly diagnosed diabetic patients and those with fasting glycaemia in the diabetes range have even worse outcomes compared to patients with known diabetes. Overall, 50% of all patients presenting with STEMI have abnormal glucose metabolism of which fewer than 50% are known diabetics. Obviously, the efficacy of reperfusion therapy in reopening the occluded artery is similar in STEMI patients with or without impaired fasting glycaemia, while the pre-existing decreased myocardial perfusion in STEMI patients with impaired fasting glycaemia persists after successful epicardial revascularisation. There is no doubt that improving microvascular perfusion within the ischaemic myocardium remains the ultimate goal of managing STEMI patients with impaired glucose metabolism. Identification of defective myocardial perfusion together with an aggressive antithrombotic regimen, reduction of the inflammatory response of the ischaemic myocardium and improvement of glycaemia control represent promising therapeutic approaches that deserve additional specific clinical investigations. This review examines all these important issues.