Cardiorenal syndrome (CRS) is a complex disease in which the heart and kidney are simultaneously affected, and subsequently the malfunction of one organ promotes the deterioration of the other. Heart failure (HF) with preserved ejection fraction (HFpEF) is the most common form of HF. The pathophysiology of CRS is not well known and several mechanisms have been involved. An elevation of central venous pressure seems to be one of the key points to consider, among others such an increase of intraabdominal pressure. Several diagnostic tools have been identified to establish the diagnosis of CRS in patients with HFpEF. Currently, the availability of biomarkers of renal and cardiac injury, the use of pulmonary ultrasound (LUS), the monitoring of the size of the inferior vena cava and the study of the renal venous pattern offer a new dimension in accurately diagnosing and quantifying organ damage in CRS. Beyond the symptomatic treatment of congestion, until recently specific therapeutic tools for patients with CRS and HFpEF were not available. Interestingly, the development of new drugs such as the angiotensin/neprilysin inhibitors and sodium-glucose cotransporter-2 (SGLT-2) inhibitors offer new therapeutic strategies with potential benefits in reduction of cardio-renal adverse outcomes in this population. Randomized clinical trials focused on patients with HFpEF are currently ongoing to delineate optimal new treatments that may be able to modify their prognosis. In addition, multidisciplinary teamwork (nephrologist, cardiologist and nurse) is expected to decrease the number of visits and the rate of hospitalizations, with a subsequent patient benefit.