Birth defects are a principal focus for clinical geneticists. Currently, there are very few nonsurgical interventions available for structural birth defects, and fundamental studies in developmental biology offer hope for future therapies. More generally, a central challenge facing medicine today is the development of strategies for organ regeneration and repair, and an important next step for regenerative medicine is to understand the mechanisms by which mammals naturally use stem cells to renew and heal tissues. I will present data from our recent work focusing on stem cells in teeth, the oral mucosa, and the gastrointestinal tract as examples of organs that undergo constant renewal. First, I will discuss our studies of the continuously growing rodent incisor, which provides a model that allows for powerful integration of investigations into how stem cells function, how they evolved, and how their behaviors are coordinated across tissues. Second, I will present recent work from our lab examining the identity of stem cells in the lining of the mouth, and third, I will discuss the response of gastrointestinal epithelial stem cells to injury. Finally, I will integrate into the talk some thoughts about the potential implications of progress in developmental and stem cell biology for the fields of clinical genetics and teratology.