Bone marrow niches are specialized microenvironments comprising a heterogeneous population of cells that support and regulate hematopoietic stem and progenitor cells. Considerable advances made in the field of hematopoiesis reveal a cross talk between cells, cytokines and neurotransmitters of the hematopoietic, immune and skeletal systems. Dynamic modulation and regulation of stem cells and their niches in response to internal and external stimuli are essential for homeostasis, host defense and repair. This review presents evidence to substantiate stem cell regulation via the "brain-bone-blood triad" beginning at the embryonic stage and continuing to adulthood.