Patients with diabetes mellitus are more likely to develop heart failure and cardiac dysfunction (with or without coronary artery disease), and the combination portends a poorer prognosis. Although the majority of treatment options in heart failure appear to be as effective in those with diabetes as in those without, less is known about the safety and effectiveness of different antidiabetic medications in the setting of heart failure. Nevertheless, it is well recognized that many patients with diabetes mellitus may develop subclinical structural heart disease prior to overt clinical presentations. Therefore, the potential of early detection (or screening) is very important to prevent the significant disease burden of heart failure in the diabetic population. In-depth investigations of the role of current and emerging strategies of metabolic modulation are promising, although the precise therapeutic targets remain elusive.