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Hypercalcemia of malignancy (HM) is the most common life-threatening metabolic complication of malignancy and affects 10 to 20% of patients with advanced cancer. In the presence of hypercalcemia, it is important to recognize co-existing conditions that could partially explain the elevation of serum calcium, like primary hyperparathyroidism. HM causes a series of symptoms, constipation, nausea and vomiting, confusion and/or stupor, polyuria and polydipsia, bone pains, which decrease quality of life. The normalization of calcemia significantly improves all these symptoms and patients return most frequently at home. Despite that, HM remains largely under diagnosed and under treated in medical praxis. HM is an emergency. Treatment of HM includes: 1) rapid rehydration of isotonic saline intravenously; 2) intravenous bisphosphonates. The most currently used bisphosphonates were clodronate and pamidronate. The increase convenience of a 15 minutes infusion, the greater efficacy and longer duration of response will make zoledronate the standard of care for HM; 3) calcitonin in addition to bisphosphonates for patients in whom serum calcium is in the life-threatening range. Corticosteroids are highly effective agents for the treatment of hematologic cancer patients with calcitriol-mediated hypercalcemia.