Diabetes mellitus is well recognized as a potent and prevalent risk factor for accelerated atherosclerosis and ischemic heart disease. However, there is also evidence of cardiac dysfunction in diabetes in the absence of coronary atherosclerosis, termed diabetic cardiomyopathy. Changes in ventricular structure and left ventricular systolic and diastolic dysfunction have all been noted even in patients with well-controlled diabetes and without overt macrovascular complications. Insulin resistance, hyperglycemia, and increased free fatty acid metabolism promote coronary microvascular disease, sympathetic nervous system dysfunction, and ventricular remodeling, and may contribute to the altered cardiac phenotype seen in diabetes. In addition to standard therapy (angiotensin-converting enzyme inhibitors and β-blockers), diabetic patients with left ventricular dysfunction are likely to benefit from targeted therapies to reduce insulin resistance and modulate substrate use.