Guidelines recommend 1 of 3 beta-blockers (bisoprolol, carvedilol, metoprolol succinate) for the treatment of systolic heart failure (HF). beta-Blockers have been established to be effective in reducing mortality in more than 20 randomized, placebo-controlled clinical trials involving more than 20,000 patients with HF. However, they are not utilized in a substantial portion of eligible HF patients, possibly because physicians are unsure of the safety and benefit of beta-blockers in special populations (women, the elderly, African Americans, patients with diabetes, and patients with atrial fibrillation). The current standard of care is to treat all heart failure (HF) patients according to the recommendations for the overall population. A review of the clinical trial data reveals that there is no evidence that one evidence-based beta-blocker is preferential over the others in women or in the elderly with HF. In contrast, carvedilol may confer greater benefit in HF patients with diabetes and atrial fibrillation as well as in African American patients. Further data are needed to provide evidence-based recommendations.