Osteoclasts are multinucleated macrophages derived from mononuclear hematopoietic myeloid cells, and their activation plays a very important role in the development and progression of inflammatory bone destruction and osteoporosis. The differentiation and function of osteoclasts are regulated by a variety of cytokines and growth factors. Previous studies have shown that transforming growth factor β1 (TGF-β1) and its downstream signal transduction proteins Smad2/3 and Smad1/5 can promote or inhibit the differentiation, development and maturation of osteoclasts, and its mechanism is related to regulating the receptor activator of nuclear factor κB ligand (RANKL)/receptor activator of nuclear factor κB factor (RANK) signaling pathway and its downstream mediators. This paper mainly reviews the roles of TGF-β1/Smad signaling pathway in the differentiation and development of osteoclasts.