Old age, female gender, hypertension (HTN), cardiac ischaemia, and arterial stiffness (AS) are the main determinants of a stiff heart, diastolic dysfunction (DD), and finally heart failure with preserved ejection fraction (HFpEF); however, several cardiac or extra-cardiac pathologies may also be involved. The combined ventricular-arterial stiffening (abnormal left ventricle-arterial coupling) is the main determinant of the increased prevalence of HFpEF in elderly persons, particularly women, and in younger subjects with HTN. Hospitalization and mortality rates in patients with HFpEF are similar to those of patients with heart failure with reduced EF (HFrEF). However, although the prognosis of HFrEF has improved over time, the optimal treatment of HFpEF remains unclear, because of the differences in the pathophysiology of the two syndromes. A number of new drugs have shown promise but they will not be commercially available for several years. For the time being, aggressive treatment of non-cardiac comorbidities is the only option available for the management of HFpEF. Treatment of anaemia, sleep disorders, chronic kidney disease, non-alcoholic fatty liver disease, atrial fibrillation, diabetes mellitus, and judicious use of diuretics are effective to some degree. Statin treatment deserves special attention, regardless of the presence of dyslipidaemia, because it has been shown, mainly in small studies, post hoc analyses, and in a large recent meta-analysis, that it is related to an improved quality of life and a reduction in HF-related mortality. We urgently need to utilize these recourses to relieve a substantial number of patients suffering from HFpEF, a disease with an ominous prognosis.