Animal and human studies demonstrate the anabolic properties of low-magnitude mechanical stimulation (LMMS) in its ability to improve bone formation by enhancing the proliferation of mesenchymal stem cells and their subsequent commitment down an osteoblastic lineage. Response to mechanical strains as low as 10μɛ have been seen, illustrating the sensitivity of mechanosensory cells to mechanotransduction pathways. Applications to the spine include treatment of osteoporosis in preparation for instrumented fusion, fracture reduction in spinal cord injury patients to slow bone mineral density loss, and bone tissue engineering and enhancement of bone-implant osseointegration for pseudarthrosis and hardware failure. This review provides an overview of the fundamentals of LMMS, highlights the cellular basis and biomechanics of how mechanical strain is translated into bone formation, and then discusses current and potential applications of these concepts to spinal disorders. Mechanical signals represent a key regulatory mechanism in the maintenance and formation of bone. Developing practical clinical applications of these mechanotransduction pathways continues to be an important area of investigation in its relation to spinal pathology.