Breast cancer frequently metastasizes to the skeleton where it usually causes bone degradation. The current therapies are directed to inhibition of osteoclasts, the bone resorbing cells. However, osteoblasts also play a role in bone loss and in sustaining tumor growth. Osteoblasts in the presence of metastatic cancer cells produce cytokines and other factors that recruit more osteoclasts. In addition they are unable to carry out their major function of repairing the bone. Other cells both resident and transient in the bone marrow compartment such as mesenchymal stem cells, T lymphoctyes, neutrophils, and megakaryocytes have been shown to be involved in the complex breast cancer‑bone microenvironment interactions. Models to experimentally study breast cancer metastases in bone include standard cell culture, three‑dimensional culture and animals.