This volume contains invited scholarly papers on the topic of molecular and integrative physiology of the musculoskeletal system. At first planned to be entirely focused on bone physiology, the volume was broadened to include papers on muscle physiology and on new paradigms such as arthritis, crossover therapeutics for bisphosphonates in cancer medicine, bone marrow stem cell research in cardiology, and systems biology and bone pathophysiology. Two main themes are discussed in the volume. The first is that the musculoskeletal system does not simply subserve the needs of locomotion and physicomechanical strength; likewise, it is not solely a reservoir for stored calcium. The second is that new paradigms of therapeutic interventions can be realized from a systems approach and from the use of crossover therapies. The skeletal system is in fact intensively involved with immunological and hormonal activity, and tapping these resources may provide more effective ways to manage disease.