One of the most striking natural examples of adult tissue plasticity in vertebrates is limb and tail regeneration in urodele amphibians. In this setting, amputation triggers the destabilization of cell differentiation and the production of progenitor cells that extensively proliferate and pattern themselves to recreate a perfect replica of the missing part. A precise understanding of which cells dedifferentiate and how plastic they become has recently begun to emerge. Furthermore, information on which developmental gene programs are activated upon injury is becoming better understood. These studies indicate that, upon injury, an unusual cohort of genes are co-expressed. The future challenge will be to link the systems for studying dedifferentiation with activation of gene expression to understand on a molecular level how cells are 'pushed backward' to regenerate a complex structure such as a limb or tail.