Physiological interactions between the nervous and immune systems with components of the local microenvironment are needed to maintain homeostasis throughout the body. Dynamic regulation of bone remodeling, hematopoietic stem cells, and their evolving niches via neurotransmitter signaling are part of the host defense and repair mechanisms. This crosstalk links activated leukocytes, neuronal, and stromal cells, which combine to directly and indirectly regulate hematopoietic stem cells. Together, interactions between diverse systems create a regulatory "brain-bone-blood triad," contributing an additional dimension to the concept of the hematopoietic stem cell niche.