Bone metastasis and skeletal complications are the major contributing factors to prostate cancer (PCa) morbidity and mortality. PCa bone metastasis tends to induce predominantly osteoblastic (bone forming) lesions, although osteolytic (bone lysing) lesions are also observed. The PCa-induced bone remodeling is due to factors secreted by PCa cells that modulate tumor stroma in a paracrine fashion. The stroma cells, mainly osteoblasts and osteoclasts, in the bone microenvironment have been shown to play critical roles in the progression of PCa in bone. Recently, bone marrow-derived mesenchymal stem cells (BM-MSCs) have been found to interact with tumor cells and play a role in tumor progression. In the bone marrow, MSCs are multipotential progenitors for osteoblasts and adipocytes. It has been proposed that during age-related osteoporosis, the balance between the osteoblast and adipocyte lineages is tilted towards increased adipocytes and decreased osteoblasts, leading to fatty bone marrow with bone loss.