Tooth enamel is a complex mineralized tissue consisting of long and parallel apatite crystals configured into decussating enamel rods.in recent years,multiple approaches have been introduced to generate or regenerate this highly attractive biomaterial characterized by great mechanical strength paired with relative resilience and tissue compatibility.In the present review,we discuss five pathways toward enamel tissue engineering,(i) enamel synthesis using physico-chemical means,(ii) protein matrix-guided enamel crystal growth,(iii) enamel surface remineralization,(iv) cell-based enamel engineering,and (v) biological enamel regeneration based on de novo induction of tooth morphogenesis.So far,physical synthesis approaches using extreme environmental conditions such as pH,heat and pressure have resulted in the formation of enamel-like crystal assemblies.Biochemical methods relying on enamel proteins as templating matrices have aided the growth of elongated calcium phosphate crystals.To illustrate the validity of this biochemical approach we have successfully grown enamel-like apatite crystals organized into decussating enamel rods using an organic enamel protein matrix.Other studies reviewed here have employed amelogeninderived peptides or self-assembling dendrimers to re-mineralize mineral-depleted white lesions on tooth surfaces.So far,cell-based enamel tissue engineering has been hampered by the limitations of presently existing ameloblast cell lines.Going forward,these limitations may be overcome by new cell culture technologies.Finally,whole-tooth regeneration through reactivation of the signaling pathways triggered during natural enamel development represents a biological avenue toward faithful enamel regeneration.In the present review we have summarized the state of the art in enamel tissue engineering and provided novel insights into future opportunities to regenerate this arguably most fascinating of all dental tissues.