Today, and looking to the future, scientific discoveries from cellular, developmental and molecular biology inform our understanding of cell, tissue and organ morphogenesis as exemplified in skin, bone, cartilage, dentine, enamel, muscle, nerve and many organs such as salivary glands and teeth. Present day biomedical science yields principles for the biomimetic design and fabrication of cells, tissues and organs. Bioengineering has become a strategy that can ‘mimic’ biological processes, and inform clinical procedures for tissue and organ replacements. The future of regenerative craniofacial biology holds enormous promise for the diagnosis and treatment of congenital birth defects, traumatic injuries, degenerative chronic diseases as well as for Mendelian single gene and complex multigene diseases and disorders. The past 50 years have heralded the completion of the human genome and the introduction of ‘personalized medicine and dentistry’, the utilization of stem cell therapy for an array of diseases and disorders, the ‘proof of principle’ to reverse select inherited diseases such as anhidrotic ectodermal dysplasia (ED), and the fruits from interdisciplinary research drawn from the diverse biomedical sciences. Looking to the future, we can readily anticipate as major goals to emphasize the clinician's role in identifying clinical phenotypes that can lead to differential diagnosis, and rejuvenate missing or damaged tissues by establishing processes for the utilization of gene, cell and/or protein therapies. The future is replete with remarkable opportunities to enhance clinical outcomes for congenital as well as acquired craniofacial malformations. Clinicians play a pivotal role because critical thinking and sound clinical acumen substantially improve diagnostic precision and thereby clinical health outcomes.

Positional information on tooth morphogenesis is investigated by the identification of when and where phenotypic markers are expressed during odontogenesis. This temporal and positional information is correlated with the instructive and permissive signaling required for both dentinogenesis and amelogenesis. Of particular interest is the establishment of a map for the cranial neural crest-derived dental papilla ectomesenchyme and the odontoblast cell lineages. The expression of ectomesenchymederived cytotactin, dentin phosphoprotein, and epithelial-derived enamel proteins was studied in mice using embryonic, fetal, and postnatal mandibular first molar tooth organ development. This review summarizes the observations in the context of instructive epithelial-mesenchymal interactions and suggests that amelogenesis imperfecta and dentinogenesis imperfecta may in part be explained by alterations in these differentiation markers. Recombinant DNA methods should facilitate future investigations of these inherited dental disorders.

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The literature of biology abounds in awe‐inspiring acts of iridescent genius. Although a law of nature is phrased in abstract language and is itself devoid of passion and sensibility, the history of its discovery may be an epic worthy of Homer, every page of which bears the stamp of the personality of people. Clearly, scientific truth can be defended by dispassionate logic, but its discovery cannot be promoted this way. The human factor in the creative equation is an important aspect. The discovery of the principles that now form the foundation of developmental craniofacial biology is a story of irony and paradox. Although much progress has been made in many scientific endeavors, many questions regarding craniofacial growth and development remain unanswered. One of the main problems encountered in studies of mammalian growth and development, specifically those dealing with developmental craniofacial biology, has been the apparent lack of application of advances in parallel fields of scientific endeavor. The time seems appropriate for commingling clinical problems with the recently acquired principles of cellular, molecular, and developmental biology.

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