Disseminated tumor cells (DTC) leave the primary tumor and reside in distant sites (e.g. bone) early in prostate cancer. Patients may harbor dormant DTC which develop into clinically overt metastasis years after radical prostatectomy. We will describe recent evidence suggesting high p38/ERK ratio, bone morphogenetic proteins, and tumor growth factor-beta 2 promote dormancy in solid tumors. Furthermore, we will discuss the possible regulation of dormancy by hematopoietic stem cell and vascular niches, and describe novel models recapitulating bone marrow metastatic latency and out- growth, 3D microvascular networks, and 3D biomatrix supportive niches in the studies of tumor cell dormancy.