Small interfering RNAs (siRNA) have enormous potential as therapeutics to target and treat various bone disor-ders such as osteoporosis and cancer bone metastases. However, effective and specifc delivery of siRNA therapeu-tics to bone and bone-specifc cells in vivo is very challenging. To realize the full therapeutic potential of siRNA intreating bone disorders, a safe and effcient, tissue- and cell-specifc delivery system must be developed. This review focuses on recent advances in bone site-specifc delivery of siRNA at the tissue or cellular level. Bone-targeted nanoparticulate siRNA carriers and various bone-targeted moieties such as bisphosphonates, oligopeptides (Asp)8and (AspSerSer)6, and aptamers are highlighted. Incorporation of these bone-seeking targeting moieties into siRNA carriers allows for recognition of different sub-tissue functional domains of bone and also specifc cell types residing in bone tissue. It also provides a means for bone-formation surface-, bone-resorption surface-, or osteoblast- specifc targeting and transportation of siRNA therapeutics. The discussion mainly focuses on systemic and local bone-specifc delivery of siRNA in osteoporosis and bone metastasis preclinical models.