Chronic heart failure is a disease with high morbidity and mortality, and its incidence is increasing rapidly worldwide. New therapies are needed that can halt or even reverse the progression of heart failure, but little progress has been made in the last 20 years. This is partly due to the fact that chronic heart failure is a heterogeneous disease with many different etiologies and clinical phenotypes. At present, a pathophysiological concept to unify these different phenotypes is missing. A prominent pathophysiological feature of chronic heart failure is diastolic dysfunction, which is almost universally present in heart failure patients. This review will examine the role and mechanisms of diastolic dysfunction in heart failure. We will study diastolic dysfunction at different levels of complexity of organization: the cardiovascular system, the heart as an organ, the myocardium as a tissue, the myocyte as a cell and the molecular aspects of diastolic dysfunction.