The calcium-sensing receptor (CaSR) plays a pivotal role in regulating systemic Ca²⁺ homeostasis and is a target for drugs designed to treat certain disorders of bone and mineral metabolism. Calcimimetics are agonists or positive allosteric modulators of the CaSR; they inhibit parathyroid hormone (PTH) secretion and stimulate renal Ca²⁺ excretion. The first calcimimetic drug is cinacalcet, a positive allosteric modulator of the CaSR that is approved for treating secondary hyperparathyroidism (HPT) in patients on renal replacement therapy and for some forms of primary HPT characterized by clinically significant hypercalcemia. Cinacalcet is also being investigated as a therapy for other hypercalcemic conditions and certain hypophosphatemic disorders. Calcilytics are CaSR inhibitors that stimulate the secretion of PTH and decrease renal excretion of Ca²⁺. Although calcilytics have failed thus far as anabolic therapies for osteoporosis, they are currently being evaluated as novel therapies for new indications involving hypocalcemia and/or hypercalciuria.