Activation of regeneration upon tissue damages requires the activation of many developmental genes responsible for cell proliferation, migration, differentiation, and tissue patterning. Ample evidence revealed that the regulation of chromatin organization functions as a crucial mechanism for establishing and maintaining cellular identity through precise control of gene transcription. The alteration of chromatin organization can lead to changes in chromatin accessibility and/or enhancer-promoter interactions. Like embryogenesis, each stage of tissue regeneration is accompanied by dynamic changes of chromatin organization in regeneration-responsive cells. In the past decade, many studies have been conducted to investigate the contribution of chromatin organization during regeneration in various tissues, organs, and organisms. A collection of chromatin regulators were demonstrated to play critical roles in regeneration. In this review, we will summarize the progress in the understanding of chromatin organization during regeneration in different research organisms and discuss potential common mechanisms responsible for the activation of regeneration response program.