Heart failure (HF) is increasing in incidence globally, and approximately half of all HF patients are women. When women and men with HF are compared, there are significant differences in disease etiology, expression, outcomes, and perhaps, response to therapy. Hypertension rather than coronary artery disease is a more important etiology of HF in women, and HF with preserved left ventricular ejection fraction (HFPEF) is more common in women. Regardless of its etiology, women have better survival and less sudden cardiac death, but poorer quality of life with equivalent degrees of left ventricular dysfunction. Animal studies of myocardial response to stressors resulting in heart failure corroborate sex differences in ventricular remodeling, cellular morphology, and function. Despite the fact that women make up nearly 50 % of HF patients, their inclusion in randomized clinical trials has remained at about 20 %, with no trials including women as a prespecified subgroup for statistical analysis. Thus, the evidence base for treatment of HF in women is not robustly supported by sex-specific data.