Less than 25 years ago tumor-induced hypercalcemia was often a lethal complication of cancer. Nowadays, it can be treated easily and successfully in at least 90% of cases by volume repletion in addition to the use of bisphosphonates that are potent anti-osteoclastic compounds. The standard therapy consists of the administration of 90 mg pamidronate or, more recently, 4 mg zoledronic acid, a more efficient bisphosphonate. When available, another alternative bisphosphonate is ibandronate. Recurrent hypercalcemia is nevertheless difficult to control and antibodies against parathyroid hormone-related protein could be useful for that matter in selected patients who are not in the terminal stage of their disease. Prevention of tumor-induced hypercalcemia is one of the objectives of long-term therapy with bisphosphonates in patients with tumor bone disease. The use of bisphosphonates in placebo-controlled trials has shown that the incidence of hypercalcemic episodes is reduced by more than one half.