Abstract Plants possess a remarkable capability to regenerate new organs after wounding. De novo root regeneration (DNRR) from aboveground tissues after physical wounding is observed in a wide range of plant species. Here, we provide an overview of recent progress in the elucidation of the molecular mechanisms that govern DNRR, with a particular emphasis on the early signaling components. Wound-inducible chemicals and hormones such as jasmonic acid, ethylene, and salicylic acid, which were originally identified as defense hormones, influence DNRR. Ongoing work elucidating the molecular network underlying DNRR provides insight into the coactivating regeneration and defense responses at the early stages of the wound response in plants.