Abstract Tooth development is initiated with placode formation followed by thickening of the oral ectoderm-derived dental epithelium. The dental epithelium then undergoes invagination into the dental mesenchyme, which is derived from the cranial neural crest. The subsequent reciprocal interactions between the dental epithelium and mesenchyme, involving a variety of molecules, are important for tooth morphogenesis, as well as for regulation of tooth number. Recent analyses of mouse mutants have provided important insights into the mechanisms underlying tooth development, including supernumerary tooth formation. In this review, we have discussed the molecular basis for the regulation of tooth number and supernumerary tooth formation.