Abnormalities in circulating levels of calcium are commonly encountered by the internist and endocrinologist. Ninety-nine percent of the body’s calcium is found in bone, with the remaining fraction in either the extracellular or intracellular compartments of all other tissues. Approximately half of the circulating blood calcium is bound to serum proteins, but it is the nonbound fraction (or ionized calcium) that is tightly controlled by the calcium homeostatic hormones. The role of calcium in many cellular functions, including the excitation of nerves and muscle and the contraction of muscle (including the myocardium), directly relates to the symptoms of both its excess and insufficiency in the circulation. Because of the physiologic importance of maintaining the blood calcium concentration in a tight range, the feedback loop that controls calcium homeostasis is highly sensitive (Fig. 1). The two main calcium regulatory hormones are parathyroid hormone (PTH) and 1,25(OH)2 vitamin D. Calcitonin’s role in human physiology is less clear. Similarly, the role, if any, of PTH-related protein (the peptide responsible for humoral hypercalcemia of malignancy) in normal physiology has not yet been elucidated.