Teeth, like all epithelial appendages, form via a sequential and reciprocal series of inductive signals between the epithelium and the underlying mesenchyme. The genes involved in this signaling network regulating ectodermal organ development have been highly conserved during evolution and are gaining more understanding in great detail. The specific functions of numerous genes during embryogenesis are known, and the involvement of their mutations in the pathogenesis of congenital defects is being extensively studied. Recently, the micro-RNA (miRNA) pathway has been associated with various aspects of embryogenesis including ectodermal organ formation and odontogenesis. In this review, I presented the genetic network involved during tooth formation and evolution, and several mutations that give rise to dental defects. The possible impact of fine-tuning and network regulation by miRNAs on development, evolution of teeth, and defects are, therefore, discussed.