Dental enamel is the most highly mineralized tissue of vertebrates and consists mainly of submicroscopic crystals of hydroxyapatite. Comparative analysis of enamel structure has revealed a marked structural diversity among vertebrates. In most cases, the enamel of amphibians and reptiles is aprismatic, since the crystallites are roughly parallel to each other and perpendicular to the enamel surface. The enamel of mammals is formed by prismatic structures, the diversity of which may be used to infer phylogenetic relationships and to identify mammalian taxa in higher orders. The complexity of enamel has been also related to feeding habits, since the patterns observed have usually evolved as functional adaptations in response to biomechanical stress imposed on teeth. In this article we review and discuss the modifications in enamel structure that occurred during mammalian evolution, as well as the functional and cellular aspects related to these changes.