Plant regeneration is widely exploited in genetic transformation, genome editing, tissue culture, cuttage, and grafting, which are crucial means to improve crop productivity and resilience. However, plant regeneration is heavily restricted by their low regeneration efficiency and genotype recalcitrance, especially in many economically important plant species. To address these challenges, new approaches have been developed to greatly improve regeneration efficiency and genotype plasticity. Among them, small molecules represent attractive options that offer an effective, inexpensive, and convenient strategy to enhance regeneration efficiency in a stepwise and controllable manner. Here, we summarize current advances in the characterization of small molecules with superior efficacy and their molecular mechanisms in plant regeneration, highlighting their advantages for fundamental studies and practical applications. Finally, we conclude with a critical discussion on the remaining questions and future challenges in pinpointing small molecules with regeneration-enhancing potential.

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