Bone is a frequent site of metastases in many cancers. Both bone properties and the tumorintrinsic traits are associated with the metastatic propensity to bone (i.e., the bone tropism). Whereas an increasing body of mechanistic studies expanded our understanding on bone tropism, they also revealed complexity across the bone lesions originated from different cancer types. In this review, we will discuss the physical, chemical, and biological properties of bone microenvironment, identify potential players in every stage of bone metastases, and introduce some of the known mechanisms regulating the bone colonization. Our objectives are to integrate the knowledge established in different biological contexts and highlight the determinants of bone tropism.