Stem cells are unspecialized precursor cells that mainly reside in the bone marrow and have important roles in the establishment of embryonic tissue. They also have critical functions during adulthood, where they replenish short-lived mature effector cells and regeneration of injured tissue. They have three main characteristics: self-renewal, differentiation and homeostatic control. In order to maintain a pool of stem cells that support the production of blood cells, stromal elements and connective tissue, stem cells must be able to constantly replenish their own number. They must also possess the ability to differentiate and give rise to a heterogeneous group of functional cells. Finally, stem cells must possess the ability to modulate and balance differentiation and self-renewal according to environmental stimuli and whole-organ needs to prevent the production of excessive number of effector cells.1 In addition to formation of these cells, regulated movement of stem cells is critical for organogenesis, homeostasis and repair in adulthood. Stem cells require specific inputs from particular environments in order to perform their various functions. Some similar trafficking mechanisms are shared by leukocytes, adult and fetal stem cells, as well as cancer stem cells.1,2 Achieving proper trafficking of stem cells will allow increased efficiency of targeted cell therapy and drug delivery.2 In addition, understanding similarities and differences in homing and migration of malignant cancer stem cells will also clarify molecular events of tumor progression and metastasis.2 This chapter focuses on the differentiation, trafficking and homing of the major types of adult bone marrow stem cells: hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) and the term "stem cell" will refer to "adult stem cells" unless otherwise specified.