Evaluation of: Song JJ, Guyette JP, Gilpin SE, Gonzalez G, Vacanti JP, Ott HC. Regeneration and experimental orthotopic transplantation of a bioengineered kidney. Nat. Med. 19(5), 646-51 (2013). Emergent technologies of regenerative medicine have shown immense potential to overcome the limitations of organ transplantation by supplying tissues and organs bioengineered ex vivo in the laboratory. So far, clinical translation has been possible for simple, hollow organs, whereas the bioengineering and regeneration of complex modular organs (namely, kidneys, hearts, livers, lungs and small bowel) remains far from our grasp. In the case of the kidney, the bioengineering and regeneration of renal organoids requires a supporting scaffold that approximates the biochemical, spatial and vascular relationships of the native kidney extracellular matrix. A recent report describes the use of rodent kidneys to generate whole organ, three-dimensional scaffolds. These scaffolds were subsequently seeded with rat neonatal kidney cells to reconstitute the parenchymal cell compartment and with human umbilical venous endothelial cells to reconstitute the endothelium and allow implantation. Once assembled and allowed to mature in bioreactors, the so-obtained constructs were able to exert some function peculiar to the kidney both in vitro and in vivo after implantation in rodents. In this invited commentary, we will address the most critical topics of organ regeneration starting from the above-mentioned experience with the kidney but eventually embracing the whole field of complex modular organs bioengineering.