This book covers our current understanding of the role of mesenchymal stem cells (MSCs) and other mesenchymal progenitors in skeletal regeneration, encompassing bone, cartilage and whole joint regeneration. The expansion reflects developments in the field to include data on the use of MSCs in drug development, growth factors, scaffolds and biomechanical manipulations for skeletal trauma and diseases, including osteoporosis and arthritis. Written for an audience of clinicians and young researchers who are exposed to MSCs in their work, this work summarizes recent findings pertaining to the definition and characterization of MSCs in skeletal tissues and discusses the mechanisms of their actions in regeneration of bone in vivo. The authors describe recent findings pertaining to the efficacy of MSC therapies in animal models and in human clinical trials and bring together literature showing that the ways MSCs are extracted, expanded and implanted can considerably affect bone formation outcomes. Finally, it presents the latest knowledge on the nature of native MSCs in skeletal tissues, which provide a platform for novel in situ tissue regeneration approaches for systemic bone disease such as osteoporosis. It focuses specifically on the use of stem cells in skeletal tissue generation for a broad audience of stem cell, cancer, and bone biologists, orthopedists, oncologists, and regenerative medicine specialists. It provides a short historical 'detour' and foundational information on founding concepts, discoveries and personalities in MSC research. It assists a new generation of scientists and clinicians in digesting the multitude of journal articles on the topic by providing easily-absorbed and condensed foundational context.