Calcium and phosphate regulate numerous biological processes and they are essential for bone mass and bone quality. The calcium and phosphate balance largely depends on intestinal absorption, and the dietary content of these ions determines the type of transport. High dietary intake of calcium and phosphate enables absorption by passive transport, but often the dietary content of these ions is in the low-normal range, especially for calcium. In this condition, the contribution of active intestinal calcium transport will increase to maintain normal serum levels. This adaptation is mainly regulated by the active form of vitamin D, 1,25 dihydroxyvitamin D, and requires normal concentrations of the precursor 25-hydroxyvitamin D. When intestinal calcium absorption is insufficient, hormonal adaptations will release calcium from bones to secure normocalcemia, not only by increasing bone loss but also by decreasing bone mineralization. These data underline the fact that adequate calcium intake is critical to secure skeletal integrity. Despite the insights that sufficient dietary calcium intake and normal 25-hydroxyvitamin D levels are critical for calcium and bone homeostasis, surprisingly little is known on the proteins that mediate intestinal calcium transport. Also, the interaction between the intestine and the kidney to control serum phosphate levels is still incompletely understood.