Patients with diabetes mellitus have an increased risk of coronary artery diseases such as myocardial infarction. Sulfonylureas are used in the treatment of diabetes mellitus and have been linked with adverse cardiovascular effects due to an apparent effect on myocardial ischemic preconditioning. Individual sulfonylureas differ pharmacologically and may have different effects. Although the hypotheses were stimulated by animal studies and experimental studies using intermediate end points, data on the possible clinical implications in humans remain sparse. However, recent data seem reassuring.