Heart failure is a complex clinical syndrome, the incidence and prevalence of which is increased in diabetes mellitus, pre-diabetes, and obesity. Although this may arise from underlying coronary artery disease, it often occurs in the absence of significant major epicardial coronary disease, and most commonly manifests as heart failure with preserved ejection fraction. Despite epidemiological evidence linking diabetes to heart failure incidence and outcome, the presence of a distinct primary "diabetic" cardiomyopathy has been difficult to prove, because the link between diabetes and heart failure is confounded by hypertension, microvascular dysfunction, and autonomic neuropathy. Nonetheless, several mechanistic associations at systemic, cardiac, and cellular/molecular levels explain different aspects of myocardial dysfunction, including impaired cardiac relaxation, compliance, and contractility. This review seeks to describe recent advances and limitations pertinent to integrating molecular mechanisms, clinical screening, and potential therapeutic avenues for this condition.