Members of the transforming growth factor-β (TGF-β) superfamily are critical regulators that control cell proliferation, differentiation and apoptosis. TGF-β signalling also regulates the morphogenesis of many developing organs. The development of mouse tooth germ, which is a good model for organogenesis, provides a powerful tool for elucidating the molecular mechanisms that control organogenesis. As ectodermal appendages, the tooth organ arises from complex and progressive interactions between an ectoderm, the oral epithelium and an underlying mesenchyme. Their morphogenesis is regulated by conserved signalling pathways, including TGF-β. In this review, the essential function of the TGF-β superfamily will be discussed in detail, including TGF-β, bone morphogenetic proteins (BMP), activin, etc, during tooth crown patterning and following tooth root development. The review also highlights recent advances in the understanding of Smad-dependent and Smad-independent pathways in regulating tissue-tissue interactions during patterning of tooth crown and root.