The delivery of mechanical signals to the skeleton using vibration is being considered as a non-drug treatment of osteoporosis. Delivered over a range of magnitudes and frequencies, vibration has been shown to be both anabolic and anti-catabolic to the musculoskeletal tissues, yet caution must be emphasized as these mechanical signals, particularly chronic exposure to higher intensities, is a known pathogen to many physiological systems. In contrast, accumulating preclinical and clinical evidence indicates that low intensity vibration (LIV) improves bone quality through regulating the activity of cells responsible for bone remodeling, as well as biasing the differentiation fate of their mesenchymal and hematopoietic stem cell progenitors. In vitro studies provide insights into the biologic mechanisms of LIV, and indicate that cells respond to these low magnitude signals through a distinct mechanism driven not by matrix strain but acceleration. These cell, animal, and human studies may represent the foundation of a safe, non-drug means to protect and improve the musculoskeletal system of the elderly, injured, and infirmed.