Most organs start their development in the early embryo from interactions between epithelial and mesenchymal cells. The nature of the signalling pathways and their downstream targets that mediate these interactions are increasingly well-understood. Mammalian teeth develop from a reciprocal series of interactions between embryonic oral epithelium and neural crest-derived mesenchyme. The first instructive signals come from the epithelial cells which act to initiate the tooth forming process and to regulate the temporo-spatial expression of transcription factor genes in the mesenchyme. These spatial domains of mesenchymal gene expression provide the positional information that determines the eventual shape of the tooth (molar, incisor etc.). By understanding the key genetic interactions that function early in tooth development in the embryo, together with the properties of the epithelial and mesenchymal cells required for them to participate in odontogenesis, stem cell-based tissue engineering approaches can be developed to recreate early embryonic tooth rudiments that can form the basis for use in humans to replace missing or damaged teeth.