Primary hyperparathyroidism is caused by excessive, abnormally regulated secretion of parathyroid hormone (PTH) from the parathyroid glands. Chronic exposure of its two principal target organs, bone and kidney, to PTH causes hypercalcemia, a major hallmark of the disease. The incidence, pathophysiology, cause, clinical manifestations, diagnostic evaluation, and therapy of primary hyperparathyroidism are discussed in this chapter. Pathology and surgical therapy are covered separately in Chapter 48 and Chapter 62, respectively.