Disorders of calcium and phosphorus homeostasis present both acute and chronic clinical consequences for newborns. The etiologies responsible range from iatrogenic, idiopathic, and inherited metabolic abnormalities. Maintenance of physiologically normal serum calcium and phosphorus requires complex interactions between the kidneys, gastrointestinal tract, and bone. Calciotropic hormones such as vitamin D and parathyroid hormone, as well as hormones controlling phosphorus homeostasis, such as fibroblast growth factor-23 (FGF-23), are essential in controlling these interactions. In newborns, calcium and phosphorus balance must necessarily be positive in order to provide the requisite building blocks for growth and maturation. Renal tubular handling of these minerals is a key control point in regulating the overall body balance in calcium and phosphorus. Adaptive changes in renal calcium and phosphorus reabsorption in newborns explain how a net positive total body balance of these minerals is achieved. Monogenetic disorders leading to abnormal renal handling of calcium and/or phosphorus have immediate clinical consequences in terms of complications associated with high or low levels of these minerals. Perhaps more importantly, chronic abnormalities of calcium and/or phosphorus, without treatment, may have serious consequences for growth and development of the growing skeleton. This article serves to review calcium and phosphorus regulation in the human body, describe differences in handling of these minerals by the newborn, and review the conditions, both acquired and congenital, that may present with abnormalities in calcium and/or phosphorus in the newborn period.