The skeleton is the most common organ to be affected by metastatic cancer. Hypercalcemia of malignancy (HM) affects 10 to 20% of patients with advanced cancer. 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. Despite that, HM remains largely underdiagnosed and undertreated. HM is an emergency. Treatment of HM includes rapid rehydration of isotonic saline and i.v. bisphosphonates. Complications from metastatic bone disease include pathological fracture, HM, spinal cord compression, bone marrow infiltration, pain, and reduced mobility. Treatment with bisphosphonates are effective to reduce these complications. They should be started when bone metastases are diagnosed and continue until it is no longer clinically relevant. 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 makes zoledronate the standard of care for HM and metastatic bone disease.