The approach to the patient with hypercalcemia requires a solid understanding of the principles of calcium homeostasis, knowledge of its differential diagnosis and the associated pathophysiologies, and the clinical judgment to know when and how to administer appropriate therapy. Recent advances in our understanding of the regulation of mineral metabolism have led to new insights into these areas and have improved our ability to deal with this rather common clinical entity. The purpose of this monograph is to give a current view of hypercalcemia as it is appreciated in the outpatient and the inpatient setting. It is designed to focus the evaluation of the hypercalcemic patient in a way that is both expedient and accurate as well as to take advantage of available therapies. A summary of the underlying physiological principles of calcium homeostasis is followed by a consideration of the complete differential diagnosis of hypercalcemia. The two most important causes of hypercalcemia, primary hyperparathyroidism and malignancy, are emphasized. Signs and symptoms of hypercalcemia are discussed with particular attention to those factors that are influential in accentuating or masking these features. Finally, an approach to the therapy of hypercalcemia is presented within a pathophysiological framework.