The bony skeleton enables the locomotive activity, the storage of calcium, and the harboring of the hematopoietic stem cells from which blood and immune cells are derived. The immune and skeletal systems share various molecules including cytokines, signaling molecules, transcription factors and membrane receptors. Investigation into rheumatoid arthritis (RA) as well as cloning of RANKL and various bone phenotypes found in immune-compromised gene deficient mice has highlighted the importance of the dynamic interplay between the both systems. These findings have recently led to both the emergence and subsequent rapid evolution of the field of osteoimmunology. The scope of osteoimmunology has been extended to encompass a wide range of molecular and cellular interactions, the elucidation of which will provide a scientific basis for future therapeutic approaches to diseases related to the immune and skeletal systems.