Tooth enamel is a fascinating tissue with exceptional biomechanical properties that allow it to last for a lifetime. In this mini review, we discuss the unique embryonic origin of this highly mineralized tissue, the complex differentiation process that leads to its "construction" (amelogenesis), and the various genetic conditions that lead to impaired enamel development in humans (amelogenesis imperfecta). Tremendous progress was made in the last 30 years in understanding the molecular and cellular mechanism that leads to normal and pathologic enamel development. However, several aspects of amelogenesis remain to be elucidated and the function of many genes associated with amelogenesis imperfecta still needs to be decoded.