The clinical relevance of diastolic dysfunction in heart failure has recently been emphasized. In fact, the presence of signs of heart failure does not imply a depressed left ventricular systolic function; moreover, the severity of heart failure and effort tolerance are more closely related to diastolic than to systolic indexes. However, the principal trials about the treatment of heart failure were mainly addressed to patients with significant left ventricular systolic dysfunction, whereas the optimal therapy for diastolic dysfunction is not well known. The aim of this review was to assess the rationale and the therapeutic options in heart failure due to diastolic dysfunction. A diastolic dysfunction can be exclusive or associated with systolic dysfunction, as in dilated cardiomyopathy. It has to be noted that in this disease an improvement of diastolic function was demonstrated for most of the drugs currently employed in the treatment of heart failure, such as vasodilators, ACE inhibitors, beta-blockers, digitalis, and other inotropic drugs. Moreover, the favorable effect of the treatment on diastolic parameters (reduction of left ventricular filling pressure, regression of restrictive filling pattern) is associated with a positive prognostic impact. The main objective of the treatment of heart failure with preserved left ventricular systolic function is to control the symptoms by means of lowering high left ventricular filling pressure without significantly lowering cardiac output. According to the therapeutic guidelines of the American College of Cardiology/American Heart Association Task Force, the drugs indicated to treat symptomatic patients with heart failure and preserved left ventricular systolic function are diuretics and nitrates. Potentially useful, but with insufficiently proven efficacy are beta-blockers, calcium antagonists and ACE inhibitors, whereas direct vasodilators and inotropic drugs were considered inadvisable. It is important to remember that the treatment might possibly be oriented to the cause and also to the possible precipitating factors of the heart failure syndrome (i.e. ischemia, tachycardia, arrhythmias, hypertension). In conclusion, considering the relatively common incidence of heart failure due to prevalent diastolic dysfunction, and the few available data about the therapeutic options in these patients, large multicenter trials devoted to the treatment of this syndrome are needed.