Nephrogenic diabetes insipidus (NDI) is a rare disease characterized by the inability of the kidney to respond to vasopressin and concentrate urine. Hereditary NDI is primarily caused by mutations in the arginine vasopressin receptor-2 (AVPR2) gene, which enables the response to antidiuretic hormone. Mutations may lead to misfolding of the mutant AVPR2 protein or its retention within the Endoplasmic reticulum of the cell. Therefore, patients cannot respond to antidiuretic hormone and concentrate urine. Consequently, in untreated patients severe dehydration and hypernatremia may occur depending on the severity of the disease. Low-sodium and protein diet, using thiazide diuretics, and amiloride treatment are the conventional and standard treatments for NDI. Besides, many in vitro functional analysis studies have been focused on pharmacological chaperones for restoring function of NDI-causing AVPR2 mutants. Vaptans, which are known as vasopressin receptor antagonists and also pharmacological chaperones, are among the current and controversial topics for developing new treatment strategies for NDI. This study aims to review the in vitro studies on vaptans which are targeted to restore expression and function of mutant AVPR2s that cause NDI and highlight the importance of their effectiveness according to the type of mutation.