Phosphate is a key component of several physiologic pathways, such as skeletal development, bone mineralization, membrane composition, nucleotide structure, maintenance of plasma pH, and cellular signaling. The kidneys have a key role in phosphate homeostasis, with 3 hormones having important roles in renal phosphate handling: parathyroid hormone, fibroblast growth factor 23 (FGF-23), and 1,25-dihydroxyvitamin D. Independent of the genetic diseases affecting the FGF-23 pathway (such as hypophosphatemic rickets), hypophosphatemia is a frequent condition encountered in daily practice, and untreated critical hypophosphatemia can induce hemolysis, rhabdomyolysis, respiratory failure, cardiac dysfunction, and neurologic impairment. Rapid correction thus is necessary to avoid severe complications. The aims of this teaching case are to summarize the causes and biological evaluation of hypophosphatemia and provide an overview of our current understanding of phosphate metabolism.