This review focuses on the pathophysiology and treatment of an increasingly common entity, cardio-renal insufficiency. Cardio-renal insufficiency is more than a simultaneous cardiac and renal disease. Patients with this condition live within a fragile equilibrium challenged by the interaction of profibrogenic, atherosclerotic, neurohumoral, and other less known factors. Regarding therapy, the avoidance of oscillations between overfilled-decompensated and emptied-overtreated states becomes of critical importance. Particular focus should be paid to personalized treatment, adjusted according to heart and kidney reserve, the predictable complications of therapy, prevention of decompensations, simple measures-based follow-up and alternative procedures.