Heart failure affects 5 million Americans, and nearly 50% of these are women. Sex differences have been noted regarding the underlying etiology, pathophysiology, and prognosis. Women are less likely to have coronary artery disease and more likely than men to have hypertension and valvular disease as the underlying etiology. They often present at an older age with better systolic function than men. For both sexes, there is significant morbidity, but age-adjusted data reveal that women have a better survival. Despite these known sex differences, medical management recommendations are the same for women and men, because prospective sex-specific clinical trials have not been performed. However, our review raises some concerns that women might respond differently to therapy.