Several studies performed before and after the introduction of fibrinolysis as a routine treatment of patients with myocardial infarction (MI) consistently showed that diabetic patients have a higher mortality in-hospital and after discharge. Women with insulin-dependent diabetes (IDD) appear to have a particularly ominous prognosis. So far, very few randomized prospective studies evaluated the effect of pharmacological treatments on prognosis of diabetic patients during acute MI: most of the information on the effect of commonly used cardiovascular drugs in diabetic patients with acute MI (AMI) has been obtained only from retrospective subgroup analyses of some of the large trials or as nonrandomized comparisons. The overview of fibrinolytic trials in acute MI found that fibrinolytic treatment was associated with a 35 days mortality of 13.6% versus 17.3% in diabetics (-21.7%) and 8.7% versus 10.2% in nondiabetics (-14.3%). Data from trials with aspirin suggest that the beneficial effect of this drug is maintained in diabetic patients with acute MI, but the optimal dosage remains undefined. Based on available evidence, beta blockers appear to be able to reduce mortality post-MI in diabetic patients, with an absolute and relative beneficial effect that is, in most cases, larger than that observed in nondiabetic patients. The pooled data from studies non beta blockers indicate a 37% mortality reduction in diabetic patients, compared to 13% in nondiabetics during the acute phase, and a 48% reduction of mortality compared to 33% in nondiabetics post-discharge. Data on outcome of diabetic patients in trials evaluating calcium antagonists are lacking, and there is a strong need for a reevaluation of data from completed trials to obtain some hints on the possible effect of these agents in this population. The "long-term" studies on angiotensin-converting enzyme (ACE) inhibitors in patients with left ventricular dysfunction some time after AMI have shown that the beneficial effect documented in the overall population is present also when limiting the analysis to patients with a history of diabetes, whereas the "acute" studies enrolling patients within 24-36 h after the onset of symptoms have shown a marked beneficial effect of ACE inhibitors in diabetic patients. For example, in the GISSI 3 study, treatment with lisinopril was associated with a decreased 6-week mortality in both IDD (11.8% versus 21.1, p < 0.05) and non-IDD (8.0% versus 10.6%, p < 0.05) patients corresponding to a 44.1% and 24.5% reduction, respectively. All these results must be taken with great caution because in no studies the effect of treatment in diabetic patients was a predefined analysis. They strongly suggest, however, that ACE inhibitors and beta blockers may be particularly beneficial during the acute phase of MI and also post-discharge, offering a strong rationale for their widespread use in diabetic patients with acute MI.