Disturbances in mineral homeostasis are common in the neonatal period, especially in premature infants and infants who are hospitalised in an intensive care unit. In many cases these disturbances are thought to be exaggerated responses to the normal physiological transition from the intrauterine environment to neonatal independence. By contrast, some disturbances in calcium homeostasis are the result of genetic defects, which in many instances can now be identified at the molecular level. In other cases hypocalcaemia or hypercalcaemia may result from pathological intrauterine conditions, birth trauma or stress, or fetal immaturity. Diagnosis and management of hypocalcaemia and hypercalcaemia in the neonate and infant requires specific knowledge of perinatal mineral physiology and the unique clinical and biochemical features of newborn mineral metabolism. In this chapter we will provide a brief overview of calcium metabolism with an emphasis on the neonatal transition, followed by discussion of the common causes of hypercalcaemia and hypocalcaemia.