Under the term cardiorenal syndrome (CRS) falls an increasing number of patients who present with combined heart and kidney dysfunction. Despite the increasing knowledge concerning CRS pathophysiology, diagnosis, and treatment, many of the aforementioned aspects remain obscure in everyday clinical practice. Some of the challenges that clinicians face when they treat CRS nowadays is the need for a patient-centered management with early diagnosis, early intervention, the distinction of true kidney injury from permissive renal function deterioration during decongestion therapy, and the development of therapeutic algorithms to guide therapy.