Diabetes is recognized as an independent risk factor for cardiovascular morbidity and mortality. This is due, in large part, to premature atherosclerosis, enhanced thrombogenicity and activation of systemic inflammatory programs with resultant vascular dysfunction. More enigmatic mechanisms underpinning diabetes-associated cardiac pathophysiology include the direct metabolic consequences of this disease on the myocardium. Nevertheless, a role for diabetes-associated disruption in cardiac contractile mechanics and in increasing cardiomyocyte susceptibility to ischemic-stress has been implicated independent of vascular pathology. This review will focus broadly on the direct effects of diabetes on the cardiac myocardium with more specific reference to the role of the modulation of cardiomyocyte mitochondrial function in these disease processes. This focus in part, stems from the growing recognition that in some instances mitochondrial dysfunction is central to the development of insulin resistance and diabetes, and in others, diabetes associated disruption in mitochondrial function exacerbates and accentuates the pathophysiology of diabetes.