Calcium (Ca) and phosphorus (P) are essential for various systemic functions, including bone mineralization. Adequate provision of Ca and P in pediatric parenteral nutrition (PN) solutions is necessary for skeletal growth and for the prevention of metabolic bone disease. The provision of adequate doses of Ca and P in pediatric PN solutions is complicated by the increased needs in preterm and term infants, solubility limitations, and venous access. Clinicians should be aware of the evidence that supports the optimal use of Ca and P in pediatric PN solutions, including studies that have evaluated dosing and solubility. The aim of this article is to review relevant literature and practices for the use of these two minerals in pediatric PN solutions. The vitamin D endocrine system, a critical component for Ca homeostasis and bone mineralization, is discussed, as well as clinical manifestations of metabolic bone disease and methods for its prevention, assessment, and treatment in pediatric patients receiving PN.