It has been well described that many patients with heart failure (HF) have a normal left ventricular ejection fraction. This entity has been termed "heart failure with preserved ejection fraction (HFPEF)". Significant advances have been made in understanding the clinical characteristics of HFPEF over the past 2 decades on the basis of large HF registries and randomized clinical trials. However, most multicenter clinical trials that investigated medical therapies in HFPEF have yielded disappointing results. HFPEF being a clinical syndrome involving multiple organ systems may be a potential explanation for treatment failure. In this review we discuss the prevalence of noncardiac comorbidities in HFPEF patients as well as their effect on the prognosis of HFPEF.