Fibroblast growth factor 23 (FGF23), a hormone primarily produced in bone cells, targets the kidney to accelerate phosphate excretion into the urine and suppresses vitamin D synthesis, thereby inducing a negative phosphate balance. Excessive serum FGF23 due to hereditary disorders such as hypophosphatemic rickets leads to phosphate wasting and impaired bone mineralization. In contrast, deficiencies in FGF23 are associated with hyperphosphatemia, elevated 1,25(OH)(2)D(3), ectopic ossification in soft tissues, and defects in skeletal mineralization. Recent studies of human genetic disorders and genetically engineered mice, as well as the in vitro approaches, have clarified some mysteries in FGF23 regulation and its potential roles in bone modeling and remodeling, which are summarized in this review article.