Along with the arrival of the first vasopressin-receptor V2R inhibitor, the indications for its use have increased. We review here and focus on polycystic kidney disease (PKD) and hyponatremia. Tolvaptan is the first drug available to slow down the progression of PKD in patients with rapid progressing disease. However, the benefits are moderate and the side effects are important, making important to share the decision of treatment together with the patient. Hyponatremia with preserved extra-cellular volume or associated with edema may be reversed by tolvaptan. Patients with SIADH or hyponatremia and edema might benefit from this treatment under strict monitoring. Overall, vaptans are helpful in several conditions, but remain tools that must be used under close control.