Hypercalcemia may decompensate from a more or less chronic status into a critical and life-threatening condition, hypercalcemic crisis. In the majority of cases, primary hyperparathyroidism is the cause; humoral hypercalcemia of malignancy or rarer conditions of hypercalcemia will decompensate less often. The leading symptoms that characterize the crisis are oliguria and anuria as well as somnolence and coma. After a hypercalcemic crisis is recognized, an emergency diagnostic program has to be followed either to prove or to exclude primary hyperparathyroidism. In the first case, surgical neck exploration is the only way to avoid fatal outcome. The diagnostic program should be performed within hours; during this time, serum calcium should be lowered. Treatment of choice is hemodialysis against a calcium-free dialysate. Bisphosphonates could be useful as adjuvant drugs.