The aerial organs of plants are highly prone to local injuries and thus require tissue regeneration to ensure their survival. However, the regenerative responses that mediate this repair are currently poorly understood. Here, Kalika Prasad and co-workers report that a feed-forward loop involving PLETHORA (PLT) genes is required for vascular regeneration in damaged Arabidopsis aerial organs. They first show that PLT3, PLT5 and PLT7 are locally induced after mechanical injury. Importantly, they reveal that regeneration in both the influorescence stem and the leaf is impaired in plt3;plt5-2;plt7 mutants, highlighting that PLT3, PLT5 and PLT7 are required for the regenerative response. The authors further show that PLT3, PLT5 and PLT7 activate the expression of CUP-SHAPED COTYLEDON2 (CUC2), which they show is also required for regeneration. In addition, polarization of the auxin transporter PIN1 is perturbed in plt3;plt5-2;plt7 mutants following injury, suggesting that PLT genes are required for correct cell polarisation and fate specification during regeneration. Finally, the researchers reveal that both CUC2 and PLTs can activate the expression of the auxin biosynthesis gene YUCCA4 (YUC4). Overall, these findings suggest that a PLT-CUC2 regulatory axis acts to induce a local hormonal environment that promotes regeneration following injury.