Although women account for a significant proportion of the growing heart failure epidemic, they have been poorly represented in clinical trials. As emerging epidemiologic data reveal a growing prevalence and burden of disease among women, it is increasingly important that treating physicians and researchers recognize sex-based differences. Despite the overall incidence of heart failure being lower in women compared with men, the magnitude of improvement in survival over the last several decades has been less apparent in women. Women with heart failure are more likely to be older, have preserved systolic function and nonischemic cardiomyopathy. While clinical trials have demonstrated improved outcomes among heart failure patients, they have predominantly included men, yielding results that are sometimes inadequately powered to detect a benefit for women. Without adequate representation of women in clinical trials, one cannot assume that the same level of therapeutic evidence also applies to women. Nonetheless, it appears that beta-blockers and angiotensin-converting enzyme inhibitors provide the same survival benefits in women with systolic dysfunction as in men. In addition, some studies suggest that angiotensin-receptor blockers may lead to a better survival in women when compared with angiotensin-converting enzyme inhibitors. Focused research is needed to understand and guide the management of women with heart failure.