Diuretic therapy, commonly used in the newborn intensive care unit, is associated with a variety of electrolyte abnormalities such as hyponatremia, hypokalemia, and hypochloremia. Hypochloremia, often ignored, is associated with significant morbidities and increased mortality in infants and adults. Clinicians respond in a reflex manner to hyponatremia than to hypochloremia. Hypochloremia is associated with nephrocalcinosis, hypochloremic alkalosis, and poor growth. Besides, the diuretic resistance associated with hypochloremia makes maintaining chloride levels in the physiological range even more logical. Since sodium supplementation counters the renal absorption of calcium and lack of evidence for spironolactone role in diuretic therapy for bronchopulmonary dysplasia (BPD), alternate chloride supplements such as potassium or arginine chloride may need to be considered in the management of hypochloremia due to diuretic therapy. In this review, we have summarized the current literature on hypochloremia secondary to diuretics and suggested a pragmatic approach to hypochloremia in preterm infants.