The acquisition and maintenance of bone mass and strength are influenced by environmental factors, including physical activity and nutrition. Among micronutrients, calcium (Ca) and inorganic (i) phosphate (P) are the two main constituents of hydroxyapatite, the bone mineral that strengthens the mechanical resistance of the organic matrix. Bone contains about 99% and 80% of the body's entire supply of Ca and P, respectively. The Ca/P mass ratio in bone is 2.2, which is similar to that measured in human milk. The initial step of Ca-Pi crystal nucleation takes place within matrix vesicles that bud from the plasma membrane of osteogenic cells and migrate into the extracellular skeletal compartment. They are endowed with a transport system that accumulates Pi inside the matrix vesicles, followed by the influx of Ca ions. This process leads to the formation of hydroxyapatite crystal and its subsequent association with the organic matrix collagen fibrils. In addition to this structural role, both Ca and Pi positively influence the activity of bone-forming and bone-resorbing cells. Pi plays a role in the maturation of osteocytes, the most abundant cells in bone. Osteocytes are implicated in bone mineralization and systemic Pi homeostasis. They produce fibroblast growth factor-23, a hormonal regulator of renal Pi reabsorption and 1,25-dihydroxy vitamin D production. This relationship is in keeping with the concept proposed several decades ago of a bone-kidney link in Pi homeostasis. In contrast to their tight association in bone formation and resorption, Ca and Pi renal reabsorption processes are independent from each other, driven by distinct molecular machineries.