Diabetic cardiomyopathy is characterized by significant changes in the physiology, structure, and mechanical function of the heart. Several molecular mechanisms have been proposed to contribute to the pathogenesis of diabetic cardiomyopathy. However, evidence for a direct, causal link between insulin resistance, a hallmark of diabetes, and ventricular dysfunction has not been established. This article discusses evidence implicating a variety of molecular targets in the pathogenesis of this disorder.