Methodologic aspects including causes of factitious hypocalcemia and hypercalcemia are summarized. The differential diagnosis of hypocalcemia is reviewed under three main headings: hypoalbuminemia, hypocalcemia with decreased parathyroid hormone (PTH) action or activity, and hypocalcemia with normal PTH action and activity. The differential diagnosis of hypercalcemia is subdivided into three broad categories: hyperproteinemia, PTH-mediated hypercalcemia, and non-PTH-mediated hypercalcemia. The causes of hypocalcemia and hypercalcemia are outlined with a focus on pathophysiology and clinicochemical sequelae. A laboratory perspective is emphasized in outlining management strategies.