The majority of men who succumb to prostate cancer (PCa) die of bone metastasis. Bone metastasis can occur years or decades after prostectomy, due to reactivation of disseminated tumor cells (DTCs) that had been dormant at the metastatic site in bone. Because treatments for bone metastasis have so far only achieved short-term disease control with excessive toxicity, preventing the tumor cells from exiting dormancy will be an innovative treatment approach, especially in PCa that occurs in the aging male population. Thus, it is critical to identify the mechanisms by which tumors enter/exit dormancy. Metastasis is attributed to properties of the tumor cells (seed) and their interaction with the microenvironment of the metastasized organs (soil). It is possible that microenvironment signaling in bone regulates the switch between proliferation and dormancy.