Patients with diabetes are at high risk for cardiovascular (CV) events and heart failure. Approximately 2–3 million diabetics in the U.S. have had a history of prior CV events. The prevalence of diabetes in patients with heart failure ranges from 24% reported in clinical trials to 47% among hospitalized patients, and an estimated 1–2 million persons in the U.S. have diabetes and heart failure. Diabetes substantially increases the risk of mortality after acute coronary syndromes and also increases the risk of hospitalizations and mortality in patients with heart failure. It is now recognized that activation of multiple neurohormonal systems is central in the pathophysiology of diabetes, CV events, and heart failure. Pharmacologic intervention in these systems (eg, angiotensin-converting enzyme (ACE) inhibition, aldosterone-receptor antagonism, and β-blockade) has been shown to decrease morbidity and mortality in diabetics with prior CV events and/or heart failure. Despite this awareness, ACE inhibitors, aldosterone antagonists, and β-blockers are underutilized, and deaths and hospitalizations caused by CV events and heart failure in diabetic patients have steadily increased. Concerns about an increased incidence of hypoglycemia, worsening dyslipidemia, and decreased insulin sensitivity resulting from the use of β-blockers may be preventing physicians from prescribing these agents for diabetic patients. β-blockade in conjunction with ACE inhibition should be standard therapy for all diabetic patients. Optimal glycemic control therapy for patients with heart failure has not been well-defined, and there is an urgent need for randomized clinical trials to determine optimal treatment.