Metastatic involvement of the bone is one of the most frequent causes of pain in cancer patients and represents one of the first signs of widespread neoplastic disease. The pain may originate directly from the bone, from nerve root compression, or from muscle spasms in the area of the lesions. The mechanism of metastatic bone pain is mainly somatic (nociceptive), even though, in some cases, neuropathic and visceral stimulations may overlap. The conventional symptomatic treatment of metastatic bone pain requires the use of multidisciplinary therapies, such as radiotherapy, in association with systemic treatment (hormonotherapy, chemotherapy, radioisotopes) with the support of analgesic therapy. Recently, studies have indicated the use of bisphosphonates in the treatment of pain and in the prevention of skeletal complications in patients with metastatic bone disease. In some patients, pharmacologic treatment, radiotherapy, and radioisotopes administered alone or in association are not able to manage pain adequately. The role of neuroinvasive techniques in treating metastatic bone pain is debated. The clinical conditions of the patient, his life expectancy, and quality of life must guide the physician in the choice of the best possible therapy.