Heart failure is a syndrome of a complex etiopathogenesis and one of the most common causes of mortality and morbidity in the world in people over the age of 65. In the past thirty years, it has been studied through many epidemiological studies, clinical randomized trials and heart failure registries that have proven the difference in response to pharmacotherapy depending on the left ventricular ejection fraction (LVEF) and stressed the need to isolate various subgroups of heart failure on that basis. Three major subgroups were included: heart failure with reduced ejection fraction (HFrEF), heart failure with a normal/preserved fraction (HFpEF) and heart failure with mid-range ejection fraction (HFmrEF). The definition of preserved or normal ejection fraction has changed over the years and for now, remains a challenge for scientists and clinicians. Patients with HFpEF do not achieve better outcomes on ACE inhibitors, ARBs, beta-blockers, and diuretics that have already been shown to reduce mortality and morbidity in HFrEF patients. HFpEF burdens more than fifty percent of heart failure patients, and therapy is mainly empirical according to comorbidities. Given the failure to investigate therapies that are effective in HFrEF patients, it was concluded that the pathophysiological mechanisms of HFpEF are different. Clinical studies were then directed to drugs that affect cGMP increase, but without success. Investigations of sacubitril/valsartan - neprilysin inhibitor in combination with ARB were the only ones that demonstrated efficacy in phase II research, and many other possibilities are being considered for the treatment of HfpEF patients.