The molecules and pathways that permit regeneration are mostly conserved between different organisms. The regulation of these pathways by the cell and/or by extrinsic factors influences its regenerative capacity. Hence deciphering the difference between the regenerating axolotl compared to the non (or less) regenerating mammals should allow us to delineate the limitations of cellular and molecular mechanisms in mammals. The final goal is to start from these differences and to develop methods which allow us to target these molecular mechanisms and boost mammalian regeneration.