The regulated migration of stem cells is critical for organogenesis during development and for tissue -homeostasis and repair during adulthood. Human bone marrow (BM) represents an accessible reservoir containing regenerative cell types from hematopoietic, endothelial, and mesenchymal-stromal lineages that together coordinate hematopoiesis and promote the repair of damaged vasculature and tissues throughout the body. Thus, a detailed understanding of lineage-specific stem cell mobilization, homing, and subsequent engraftment in areas of injury or disease is of critical importance to the rational development of novel cell-mediated regenerative therapies. Stem cell trafficking via the circulation from site of origin to peripheral tissues requires fundamental molecular pathways governing (1) niche-specific deadhesion of progenitor cells; (2) chemoattraction to guide progenitor cell homing; and (3) interstitial navigation and adhesion/retention of recruited progenitor cells. This overview chapter summarizes the diversity of migratory strategies employed by hematopoietic, endothelial, and mesenchymal-stromal progenitor cells during repair and regeneration after tissue damage. Further elucidation of stem cell homing and migration pathways will allow greater application of stem cells for targeted cell therapy and/or drug delivery for tissue repair. Strikingly similar migratory mechanisms appear to govern the in vivo migration of recently characterized cancer stem cells (CSC) in leukemias and solid tumors, indicating that conserved principles of stem cell migration and niche specificity will provide new information to target CSC in anticancer therapy.