Bone metastasis is one of the most common causes of skeletal morbidity in patients with advanced cancer and is manifested as osteoblastic and osteolytic lesions. Bone metastasis occurs as an organized and multistep process involving tumor intravasation and the survived tumor cells in circulation. Extravasation into the secondary site, initiation of tumorgenesis and angiogenesis are also included in developing the bone metastasis. Several studies demonstrated that Zoledronic acid, which belongs to the second generation of BP (nitrogen-containing BPs) class agents, is an important and well-established drug in the treatment of wide range of cancer patients, such as breast cancer, prostate cancer, and multiple myeloma associated with bone metastases.