Histological and cytological organization confer specificity to the odontoblasts. These postmitotic, neural crest derived, polarized cells are aligned in a single layer at the periphery of the dental pulp and secrete the organic components of predentin-dentin. The developmental history of these cells demands a cascade of epigenetic signalling events comprising the acquisition of odontogenic potential by neural crest cells, their patterning in the developing jaws, the initiation of odontogenesis through interaction with the oral epithelium, commitment, and tooth-specific spatial distribution of competent preodontoblasts able to overtly differentiate. Recent experimental investigations are critically summarized, many open questions are stressed, and current hypotheses concerning the control of terminal odontoblast differentiation are outlined.