Abstract Limb regeneration is an excellent model for understanding organ reconstruction along PD, AP and DV axes. Re-expression of genes involved in axial pattern formation is essential for complete limb regeneration. The cellular positional information in the limb blastema has been thought to be a key factor for appropriate gene re-expression. Recently, it has been suggested that epigenetic mechanisms have an essential role in development and regeneration processes. In this review, we discuss how epigenetic mechanisms may be involved in the maintenance of positional information and the regulation of gene re-expression during limb regeneration.