Bone is one of the most preferential metastatic target sites for cancers such as breast, prostate and lung cancers. Although the precise molecular mechanism underlying this preference needs to be elucidated, bone appears to possess unique biological microenvironments that allow circulating cancer cells to home, proliferate and survive. As a consequence of cancer expansion, cellular and molecular homeostasis of bone microenvironments is disturbed and bone is destroyed, leading to the development of bone metastases. Thus, understanding of the crosstalk between cancer cells and bone is critical to design mechanism-based effective and specific therapeutic interventions for bone metastases.