We present a case of a 29-year-old woman with a long history of nocturnal enuresis who developed symptomatic hyponatremia from water intoxication shortly after beginning desmopressin. A MEDLINE search in the English language revealed 13 prior case reports. All patients presented with seizure, mental status changes, or both. Two distinct presentations occurred: one group of patients maintained a stable course with desmopressin and developed symptoms related to an outside factor. The other group of patients were new to desmopressin and had a profound water intoxication response from its use. While the underlying cause was from simple overhydration, the quickness of this unanticipated adverse effect is noteworthy. The importance of counseling to ensure a family's and a patient's understanding of the effects of desmopressin as well as monitoring electrolytes periodically may help identify and prevent this serious iatrogenic complication.