Nephrogenic diabetes insipidus (NDI) is a disorder that involves the late distal tubules and collecting ducts, which are unresponsive to endogenous vasopressin, resulting in an inability to concentrate urine. This clinically manifests as polydipsia and polyuria in patients. Collecting duct cells express aquaporin-2 (AQP2) channels on their luminal surface that are key in regulating body water balance. The peptide hormone arginine vasopressin (AVP), released by the posterior pituitary, operates these channels through activation of the type 2 vasopressin receptor (AVPR2). Dysfunction or dysregulation of either the AQP2 channels or the receptor AVPR2 results in NDI. NDI may be congenital or acquired secondary to other conditions, including drugs. In this chapter, we discuss a case of a child with congenital NDI initially thought to have central DI and briefly review the literature.