Gender differences in the syndrome of heart failure (HF) occur in etiology and pathophysiology, in the clinical presentation and course of the syndrome. In addition, gender specific treatment responses and gender associated differences in the behavior of treating physicians are found. Hypertension and diabetes play a major role as causes of HF in women and both interact in their pathophysiology with the renin angiotensin system (RAS). Modulation of the RAS by estrogens explains specific differences between pre- and postmenopausal women and men. Myocardial growth processes and myocardial calcium handling are differentially regulated in female and male myocytes. Myocardial remodeling with age and as a consequence of mechanical load differs in women and men. For yet unknown reasons, HF with preserved systolic function seems to be more frequent in women than in men and the clinical course of systolic failure is different in both genders.