Infants consume most of their calories as formula. Because of this large fluid intake, infants normally produce dilute urine, not far off from that seen in individuals with diabetes insipidus (DI). Infants with DI are therefore prone to water intoxication if fixed antidiuresis is achieved using the long-acting vasopressin analog desmopressin (DDAVP), which induces a state of high urine concentration. DI treatment approaches applied to older children and adults, who consume the their calories as solids, are difficult to apply to infants with DI. When used in infants, oral and intranasal DDAVP can be associated with wide swings in serum sodium concentration (SNA). In comparison, precisely administered subcutaneous doses of DDAVP can be successfully used in infants with DI, and appear to be superior to oral or intranasal DDAVP therapy. Alternatively, consistent eunatremia can be simply achieved in infantile DI using low renal solute load (RSL) formula and thiazide diuretics. Low RSL formula reduces obligatory urinary water losses, and thiazide diuretics concentrate the urine to levels seen in normal formula-fed infants. This report addresses treatment options of DI in infancy and the delicate management issues involved.