Teeth are typical examples of organs in which genes determine the progress of development from initiation to the final shape, size and structure, whereas environmental factors play a minor role. Advances in gene technology over the last three decades have led to powerful novel methods to explore the mechanisms of embryonic development. Today we know a few hundred genes that regulate tooth development, and mutations in dozens of these genes have been shown to cause aberrations in tooth development in mice and/or humans. The functions of an increasing number of genes in tooth development have been discovered using genetically modified mouse models. We are now beginning to understand the ‘programme’ underlying the process of tooth formation. Key components of the programme are signals mediating communication between cells and complex gene regulatory networks in which the signal pathways are integrated. Understanding the mechanisms of tooth development at the level of genes, cells and molecules will lay the basis for new ways to prevent and treat dental defects and diseases. Over the last decade knowledge about dental stem cells has accumulated rapidly and novel stem cell technologies have been developed. Combining stem cell research with knowledge on the mechanisms of tooth development may open up novel possibilities for clinical tooth regeneration.